1 00:00:00,090 --> 00:00:02,490 The following content is provided under a Creative 2 00:00:02,490 --> 00:00:04,030 Commons license. 3 00:00:04,030 --> 00:00:06,330 Your support will help MIT OpenCourseWare 4 00:00:06,330 --> 00:00:10,690 continue to offer high quality educational resources for free. 5 00:00:10,690 --> 00:00:13,320 To make a donation or view additional materials 6 00:00:13,320 --> 00:00:17,280 from hundreds of MIT courses, visit MIT OpenCourseWare 7 00:00:17,280 --> 00:00:20,460 at ocuMIT.edu. 8 00:00:20,460 --> 00:00:24,750 ABBY NOYCE: OK so we're going to talk about Alzheimer's disease. 9 00:00:24,750 --> 00:00:29,000 Who here knows somebody who has or had Alzheimer's disease? 10 00:00:29,000 --> 00:00:31,090 Anyone with family members? 11 00:00:31,090 --> 00:00:31,590 No. 12 00:00:31,590 --> 00:00:41,280 [BACKGROUND CONVERSATION] 13 00:00:41,280 --> 00:00:44,950 Yeah, I'm lucky nobody in my family has it. 14 00:00:44,950 --> 00:00:46,590 Anyway, so Alzheimer's disease is 15 00:00:46,590 --> 00:00:51,450 part of a group of mental disorders known as dementias. 16 00:00:51,450 --> 00:00:57,180 So dementias are a group of disorders, 17 00:00:57,180 --> 00:01:00,610 diseases that are characterized by cognitive and behavioral 18 00:01:00,610 --> 00:01:01,110 deficits. 19 00:01:01,110 --> 00:01:07,680 So people's ability to think, remember, learn as well as they 20 00:01:07,680 --> 00:01:10,140 used to declines. 21 00:01:10,140 --> 00:01:15,930 This also is depending on which dementia we're discussing, 22 00:01:15,930 --> 00:01:18,370 people's ability, for example, to take care of themselves, 23 00:01:18,370 --> 00:01:22,380 to generally participate in their daily life declines. 24 00:01:22,380 --> 00:01:26,075 Dementias are usually characterized by gradual onset. 25 00:01:26,075 --> 00:01:28,200 So they start off with just a little bit of decline 26 00:01:28,200 --> 00:01:30,120 and get worse over time. 27 00:01:30,120 --> 00:01:30,930 They're chronic. 28 00:01:30,930 --> 00:01:31,680 They're permanent. 29 00:01:31,680 --> 00:01:33,980 This isn't something that you have and then get rid of. 30 00:01:33,980 --> 00:01:39,191 Dementias are lifelong once you develop one. 31 00:01:39,191 --> 00:01:41,190 In the clinical world, you make this distinction 32 00:01:41,190 --> 00:01:44,100 between dementias which are these slow onset 33 00:01:44,100 --> 00:01:47,370 chronic disorders and what are called deliriums. 34 00:01:47,370 --> 00:01:49,290 So a delirium is acute. 35 00:01:49,290 --> 00:01:53,670 It happens it's a quick change in cognitive ability. 36 00:01:53,670 --> 00:01:55,320 Working with an older adult population, 37 00:01:55,320 --> 00:01:58,440 you'll usually see delirium brought on by sometimes 38 00:01:58,440 --> 00:02:01,410 by trauma, sometimes by a medication or a medication 39 00:02:01,410 --> 00:02:02,649 interaction. 40 00:02:02,649 --> 00:02:05,190 And all of these are things that cause older adults to end up 41 00:02:05,190 --> 00:02:06,570 in the ER for some reason. 42 00:02:06,570 --> 00:02:09,750 Somebody looks up and says, Grandma is acting weird. 43 00:02:09,750 --> 00:02:11,495 Today something changed. 44 00:02:11,495 --> 00:02:12,870 Take her, put Grandma in the car, 45 00:02:12,870 --> 00:02:14,203 bring her to the emergency room. 46 00:02:14,203 --> 00:02:19,320 First thing the ER doc says, is have Grandma's 47 00:02:19,320 --> 00:02:20,670 medications change recently? 48 00:02:20,670 --> 00:02:23,460 This is a big cause of a lot of short term 49 00:02:23,460 --> 00:02:25,774 changes in older adults. 50 00:02:25,774 --> 00:02:26,940 But dementias are different. 51 00:02:26,940 --> 00:02:30,257 Dementias are usually caused by a bunch of things. 52 00:02:30,257 --> 00:02:32,090 They can be caused by a progressive disease. 53 00:02:32,090 --> 00:02:33,780 They can be caused by trauma. 54 00:02:33,780 --> 00:02:36,510 They can be caused by a stroke. 55 00:02:36,510 --> 00:02:38,490 And overall, different categories of these 56 00:02:38,490 --> 00:02:41,800 affect about 4 million people in this country. 57 00:02:41,800 --> 00:02:44,100 And that's almost all people over age 65. 58 00:02:44,100 --> 00:02:46,490 AUDIENCE: What could be a trauma? 59 00:02:46,490 --> 00:02:50,310 ABBY NOYCE: Trauma can be like a head injury or a stroke, 60 00:02:50,310 --> 00:02:51,895 something that's kind of-- 61 00:02:51,895 --> 00:02:53,520 it's not so much a disease as something 62 00:02:53,520 --> 00:02:58,300 has caused sudden death of some sort to cell in brain. 63 00:03:05,940 --> 00:03:08,890 So Alzheimer's is a particular subset of dementia. 64 00:03:08,890 --> 00:03:11,300 It's by far the most common one. 65 00:03:11,300 --> 00:03:15,522 It was first described in 1907 Alois Alzheimer. 66 00:03:15,522 --> 00:03:16,980 He was talking about a patient he'd 67 00:03:16,980 --> 00:03:19,950 been working with for about six years at that point who 68 00:03:19,950 --> 00:03:22,880 had a strange form of senile dementia. 69 00:03:22,880 --> 00:03:25,860 And it's been known kind of casually 70 00:03:25,860 --> 00:03:28,350 for a long time and more specifically more 71 00:03:28,350 --> 00:03:30,300 recently that as people get older, 72 00:03:30,300 --> 00:03:32,880 in general just in normal aging, your cognitive abilities 73 00:03:32,880 --> 00:03:33,450 decline. 74 00:03:33,450 --> 00:03:36,360 Older adults do poorer on a lot of memory tasks. 75 00:03:36,360 --> 00:03:40,020 They're slower at a lot of reflex reaction time tasks. 76 00:03:40,020 --> 00:03:41,520 In general, your cognitive abilities 77 00:03:41,520 --> 00:03:45,465 slow down as people pass into their 50s, 60s, and beyond. 78 00:03:48,330 --> 00:03:50,410 Alzheimer's is different. 79 00:03:50,410 --> 00:03:53,070 It's more than anything, it's these same deficits 80 00:03:53,070 --> 00:03:53,994 taken to an extreme. 81 00:03:53,994 --> 00:03:56,160 And we'll talk a little bit about exactly what kinds 82 00:03:56,160 --> 00:04:01,002 of changes you'll see in patients who have Alzheimer's. 83 00:04:01,002 --> 00:04:02,460 Alzheimer's accounts for, depending 84 00:04:02,460 --> 00:04:06,180 on whose estimate you ask, between 50% and 70% of all 85 00:04:06,180 --> 00:04:07,147 dementias. 86 00:04:10,200 --> 00:04:11,880 Because it correlates with lifespan 87 00:04:11,880 --> 00:04:14,046 so well as people get older, your chances of getting 88 00:04:14,046 --> 00:04:17,160 Alzheimer's increase, it's more common in countries 89 00:04:17,160 --> 00:04:18,420 with longer lifespans. 90 00:04:18,420 --> 00:04:21,120 So it's much more common in places like the US and Western 91 00:04:21,120 --> 00:04:24,930 Europe than it is, for example, in like central Africa 92 00:04:24,930 --> 00:04:27,390 just because we've got so many more adults who make it 93 00:04:27,390 --> 00:04:29,640 into their 60s, 70s, 80s-- 94 00:04:29,640 --> 00:04:32,830 these periods where the incidence starts going way up. 95 00:04:36,750 --> 00:04:38,900 All right, so how do you diagnose this? 96 00:04:38,900 --> 00:04:42,160 So in order to get a definitive diagnosis 97 00:04:42,160 --> 00:04:47,709 of Alzheimer's disease, this can only be done by autopsy. 98 00:04:47,709 --> 00:04:49,750 But there's a bunch of criteria for making what's 99 00:04:49,750 --> 00:04:51,610 called a clinical diagnosis-- a diagnosis 100 00:04:51,610 --> 00:04:54,850 you can make while people are still alive 101 00:04:54,850 --> 00:04:58,051 and say that you have Alzheimer's disease. 102 00:04:58,051 --> 00:04:59,300 Why would you want to do this? 103 00:04:59,300 --> 00:05:00,800 Why isn't it just good enough to say 104 00:05:00,800 --> 00:05:02,240 you have some kind of dementia? 105 00:05:02,240 --> 00:05:04,060 Well, one of the biggest reasons is 106 00:05:04,060 --> 00:05:06,610 that the progression of different forms of dementia 107 00:05:06,610 --> 00:05:07,940 is different. 108 00:05:07,940 --> 00:05:10,720 So the time span that you are likely to have, 109 00:05:10,720 --> 00:05:12,907 how fast the decline is likely to be 110 00:05:12,907 --> 00:05:14,740 varies across different kinds of dimensions. 111 00:05:14,740 --> 00:05:19,640 And being able to say which one someone has helps them 112 00:05:19,640 --> 00:05:22,070 and their families kind of figure out what's going on, 113 00:05:22,070 --> 00:05:23,028 what happens with this. 114 00:05:23,028 --> 00:05:26,300 And in a clinical care setting, that's really important. 115 00:05:26,300 --> 00:05:30,310 So the clinical criteria for Alzheimer's disease, and these 116 00:05:30,310 --> 00:05:31,390 are kind of in flux. 117 00:05:31,390 --> 00:05:37,690 But this is the American Psychological Association's 118 00:05:37,690 --> 00:05:41,010 current round of diagnostic criteria. 119 00:05:41,010 --> 00:05:43,090 And so to be diagnosed with Alzheimer's disease, 120 00:05:43,090 --> 00:05:46,690 patients have to have multiple cognitive deficits. 121 00:05:46,690 --> 00:05:49,600 They have to have memory impairment, which 122 00:05:49,600 --> 00:05:52,450 is kind of the classic thing that everybody knows about 123 00:05:52,450 --> 00:05:53,450 for Alzheimer's disease. 124 00:05:53,450 --> 00:05:54,670 Alzheimer's disease, if you lose your memory, 125 00:05:54,670 --> 00:05:57,250 you lose your ability to learn new information in particular. 126 00:06:01,360 --> 00:06:03,310 Patients also have to have at least one 127 00:06:03,310 --> 00:06:06,320 of the second group of cognitive deficits. 128 00:06:06,320 --> 00:06:09,790 So remember aphasia is a group of disorders in which people 129 00:06:09,790 --> 00:06:12,820 have a hard time with language, with understanding or producing 130 00:06:12,820 --> 00:06:13,890 language. 131 00:06:13,890 --> 00:06:17,230 Apraxia refers to a difficulty in making 132 00:06:17,230 --> 00:06:21,460 smooth movements and motor coordination and control. 133 00:06:21,460 --> 00:06:24,750 Agnosia-- go back a couple of weeks the agnosias are 134 00:06:24,750 --> 00:06:27,100 our class of disorders which people have difficulty 135 00:06:27,100 --> 00:06:31,060 recognizing visually presented objects and describing 136 00:06:31,060 --> 00:06:33,610 or interacting with visually presented stimuli in various 137 00:06:33,610 --> 00:06:35,170 ways-- 138 00:06:35,170 --> 00:06:38,920 or difficulties in executive function. 139 00:06:38,920 --> 00:06:43,630 What kinds of activities is executive function refer to? 140 00:06:43,630 --> 00:06:46,440 That's stuff like goal directed behavior, 141 00:06:46,440 --> 00:06:50,680 planning cause and effect reasoning-- all of this 142 00:06:50,680 --> 00:06:53,170 comes under this executive control heading. 143 00:06:53,170 --> 00:06:58,320 And so you also see patients who have difficulty with this. 144 00:06:58,320 --> 00:07:00,500 One of classic examples of this is-- 145 00:07:02,917 --> 00:07:05,000 there's some classic research working with babies, 146 00:07:05,000 --> 00:07:08,412 like six-month-old babies where you show them 147 00:07:08,412 --> 00:07:10,370 an object like a brightly colored little puppet 148 00:07:10,370 --> 00:07:12,286 or something-- something that the kid would be 149 00:07:12,286 --> 00:07:14,060 interested in and attracted to. 150 00:07:14,060 --> 00:07:17,610 And you show the kid this. 151 00:07:17,610 --> 00:07:20,430 Then they'll reach and then you put it into a box. 152 00:07:20,430 --> 00:07:23,240 And they'll reach for the box that they 153 00:07:23,240 --> 00:07:25,610 saw you put the puppet in. 154 00:07:25,610 --> 00:07:30,410 And even if you then show the experimenter picking up 155 00:07:30,410 --> 00:07:32,920 the thing and moving it to a different box 156 00:07:32,920 --> 00:07:34,880 so there's like two boxes in front of the kid, 157 00:07:34,880 --> 00:07:36,980 they'll keep reaching towards the original one, the one 158 00:07:36,980 --> 00:07:38,180 that they saw go into first. 159 00:07:38,180 --> 00:07:42,140 They don't seem to have the ability 160 00:07:42,140 --> 00:07:44,840 to take the information about how the thing moved from place 161 00:07:44,840 --> 00:07:47,030 one to place two and translate that 162 00:07:47,030 --> 00:07:49,820 into a change in how they want to direct their motor 163 00:07:49,820 --> 00:07:51,470 abilities. 164 00:07:51,470 --> 00:07:53,300 They don't have the ability to kind of take 165 00:07:53,300 --> 00:07:55,082 the reach for this box instruction 166 00:07:55,082 --> 00:07:57,290 and transform it into a reach for that box over there 167 00:07:57,290 --> 00:07:59,210 because the doll got moved instruction. 168 00:07:59,210 --> 00:08:06,770 So little six-month-old babies make this mistake. 169 00:08:06,770 --> 00:08:11,540 Patients with Alzheimer's will also make this mistake. 170 00:08:11,540 --> 00:08:18,020 So patients with moderately advanced Alzheimer's will 171 00:08:18,020 --> 00:08:20,810 make similar errors in-- 172 00:08:20,810 --> 00:08:24,200 probably not in brightly colored puppets but in a look for this, 173 00:08:24,200 --> 00:08:27,140 see it move, and then have to transition your search 174 00:08:27,140 --> 00:08:29,497 tasks to a new area. 175 00:08:29,497 --> 00:08:31,080 They seem to have a hard time with it. 176 00:08:31,080 --> 00:08:33,980 So that's an example of an executive control function 177 00:08:33,980 --> 00:08:38,507 that's hindered, that's impaired in patients with Alzheimer's. 178 00:08:42,330 --> 00:08:45,930 The other big criteria for anything like this 179 00:08:45,930 --> 00:08:50,280 is that the way the DSM, the Diagnostic and Statistical 180 00:08:50,280 --> 00:08:54,660 Manual, works is that in order to qualify 181 00:08:54,660 --> 00:08:57,090 as having a disorder of any kind, 182 00:08:57,090 --> 00:08:58,660 you've got to have impairment. 183 00:08:58,660 --> 00:09:01,350 If you are finding that your memory is declining 184 00:09:01,350 --> 00:09:04,046 and yet it is not messing up your daily life at all, 185 00:09:04,046 --> 00:09:05,670 DSM will say you don't have a disorder. 186 00:09:05,670 --> 00:09:08,460 You are working just fine. 187 00:09:08,460 --> 00:09:11,960 You are not having a disorder. 188 00:09:11,960 --> 00:09:16,010 So one of these criteria is a impairment 189 00:09:16,010 --> 00:09:18,920 in function compared to the previous level of function. 190 00:09:18,920 --> 00:09:21,560 So this is going to vary for different people 191 00:09:21,560 --> 00:09:24,320 depending on how high their cognitive abilities were 192 00:09:24,320 --> 00:09:26,957 before the onset of symptoms. 193 00:09:26,957 --> 00:09:29,290 And the other requirement is that this is, like we said, 194 00:09:29,290 --> 00:09:31,130 a gradual impairment. 195 00:09:31,130 --> 00:09:34,190 This is not an acute sudden change in cognitive ability. 196 00:09:34,190 --> 00:09:36,580 It's gradual, and it's progressive. 197 00:09:36,580 --> 00:09:38,090 It gets worse over time. 198 00:09:53,060 --> 00:09:55,220 So what does this progressiveness look like? 199 00:09:55,220 --> 00:10:01,440 So most people break Alzheimer's into four main stages. 200 00:10:01,440 --> 00:10:03,950 The first of which is what's called pre-dementia. 201 00:10:03,950 --> 00:10:06,920 And in pre-dementia stage, most people 202 00:10:06,920 --> 00:10:08,824 aren't diagnosed at this stage. 203 00:10:08,824 --> 00:10:11,240 It's hard to tell the difference between cognitive decline 204 00:10:11,240 --> 00:10:13,550 that's due to Alzheimer's disease 205 00:10:13,550 --> 00:10:16,010 from what kind of your normal aging cognitive 206 00:10:16,010 --> 00:10:18,680 decline that you're going to see in just about all adults 207 00:10:18,680 --> 00:10:21,780 in their 60s and 70s. 208 00:10:21,780 --> 00:10:25,680 But on the other hand, if you have people take, 209 00:10:25,680 --> 00:10:29,990 for example, an IQ test every year starting at 65 on. 210 00:10:29,990 --> 00:10:32,990 And when they're 80 they become diagnosed with Alzheimer's, you 211 00:10:32,990 --> 00:10:34,790 can go back and look at their older tests. 212 00:10:34,790 --> 00:10:36,248 And you can see evidence that there 213 00:10:36,248 --> 00:10:41,819 was cognitive decline over the preceding five to seven years. 214 00:10:41,819 --> 00:10:43,610 But it's not strong enough for it to really 215 00:10:43,610 --> 00:10:49,380 be diagnosed as being a dementia of any kind. 216 00:10:49,380 --> 00:10:52,250 So the next stage after the dementia 217 00:10:52,250 --> 00:10:54,480 is what's called early dementia. 218 00:10:54,480 --> 00:10:56,270 And this is usually when it gets noticed, 219 00:10:56,270 --> 00:10:57,260 when it gets diagnosed. 220 00:10:57,260 --> 00:10:59,960 You'll see that people's impairments for memory 221 00:10:59,960 --> 00:11:02,874 and for learning new information are severe enough 222 00:11:02,874 --> 00:11:04,790 that they'll go, they'll talk to their doctor. 223 00:11:04,790 --> 00:11:08,259 They'll say, hey, I'm concerned about this. 224 00:11:08,259 --> 00:11:09,800 And they're specifically bad about it 225 00:11:09,800 --> 00:11:11,300 learning new information. 226 00:11:11,300 --> 00:11:13,880 Childhood memories aren't impaired at this point. 227 00:11:13,880 --> 00:11:16,040 Semantic knowledge, knowledge about the world 228 00:11:16,040 --> 00:11:17,480 is not usually impaired. 229 00:11:17,480 --> 00:11:19,790 This is the where did I put my keys 230 00:11:19,790 --> 00:11:21,080 stage of Alzheimer's disease. 231 00:11:21,080 --> 00:11:22,413 It's a new piece of information. 232 00:11:22,413 --> 00:11:25,070 It's something from earlier today. 233 00:11:25,070 --> 00:11:26,300 But it's just not there. 234 00:11:26,300 --> 00:11:32,290 They can't pull this up 235 00:11:32,290 --> 00:11:35,620 Next step is moderate dementia. 236 00:11:35,620 --> 00:11:38,790 And at this stage, this is where you start seeing severe speech 237 00:11:38,790 --> 00:11:39,790 and language impairment. 238 00:11:39,790 --> 00:11:42,576 People can't pull out the knowledge about which words. 239 00:11:42,576 --> 00:11:44,450 They want to use their vocabulary effectively 240 00:11:44,450 --> 00:11:48,790 shrinks a lot more obscure words they just can't access anymore. 241 00:11:48,790 --> 00:11:52,420 You see deterioration in motor control. 242 00:11:52,420 --> 00:11:55,760 People have a hard time making smooth, coordinated movements. 243 00:11:55,760 --> 00:12:00,580 People have serious impairment. 244 00:12:00,580 --> 00:12:02,350 They start losing long term memory. 245 00:12:02,350 --> 00:12:04,867 They start not being able to remember things 246 00:12:04,867 --> 00:12:05,950 from when they were young. 247 00:12:05,950 --> 00:12:09,610 They start not being able to remember facts about the world. 248 00:12:09,610 --> 00:12:11,620 They start not recognizing family members, which 249 00:12:11,620 --> 00:12:13,690 is kind of another classic Alzheimer's symptom 250 00:12:13,690 --> 00:12:18,707 that people have a hard time dealing with. 251 00:12:18,707 --> 00:12:20,290 This is the stage where usually people 252 00:12:20,290 --> 00:12:23,560 start having a really hard time taking care of themselves. 253 00:12:23,560 --> 00:12:26,616 Usually in that early dementia state, 254 00:12:26,616 --> 00:12:28,990 you'll see individuals with Alzheimer's usually moving in 255 00:12:28,990 --> 00:12:30,310 with a family member. 256 00:12:30,310 --> 00:12:31,570 They're pretty much OK. 257 00:12:31,570 --> 00:12:32,560 They can get around. 258 00:12:32,560 --> 00:12:33,726 They can handle their stuff. 259 00:12:33,726 --> 00:12:36,664 But often, family doesn't want them to live alone. 260 00:12:36,664 --> 00:12:38,080 And in this modern dementia state, 261 00:12:38,080 --> 00:12:40,966 that starts being really hard all around. 262 00:12:40,966 --> 00:12:42,340 These are patients who are having 263 00:12:42,340 --> 00:12:48,582 a hard time, for example, cooking and feeding themselves. 264 00:12:48,582 --> 00:12:51,040 They might have start having a hard time tying their shoes. 265 00:12:51,040 --> 00:12:53,622 They might say they're having a hard time taking a shower. 266 00:12:53,622 --> 00:12:56,080 All of these are things which the people who they're living 267 00:12:56,080 --> 00:12:58,850 with have to help them with. 268 00:12:58,850 --> 00:13:03,460 So Alzheimer's is probably the biggest reason 269 00:13:03,460 --> 00:13:08,650 for adults to be in a caregiver relationship with another adult 270 00:13:08,650 --> 00:13:10,600 not counting like raising children. 271 00:13:10,600 --> 00:13:15,400 But when you find people taking care of a sibling or a parent 272 00:13:15,400 --> 00:13:18,250 or grandparent, it's usually due to what some kind of dementia. 273 00:13:21,286 --> 00:13:23,410 The other thing that tends to happen in Alzheimer's 274 00:13:23,410 --> 00:13:26,470 that's really distressing for family members 275 00:13:26,470 --> 00:13:31,090 is that in this moderate stage dementia 276 00:13:31,090 --> 00:13:34,886 that you start seeing affective changes. 277 00:13:34,886 --> 00:13:36,760 You start seeing mood and personality changes 278 00:13:36,760 --> 00:13:38,150 in these patients. 279 00:13:38,150 --> 00:13:42,880 So people will start to become aggressive, angry, loud, 280 00:13:42,880 --> 00:13:44,707 violent towards family members. 281 00:13:44,707 --> 00:13:46,540 They'll push, they'll shove, they'll holler. 282 00:13:46,540 --> 00:13:50,127 They'll say things that are completely inappropriate. 283 00:13:50,127 --> 00:13:51,710 And as you might imagine, for somebody 284 00:13:51,710 --> 00:13:54,790 who's giving up like all of their free time 285 00:13:54,790 --> 00:13:58,132 and a good chunk of their general sanity in the world 286 00:13:58,132 --> 00:13:59,590 to take care of this family member, 287 00:13:59,590 --> 00:14:02,780 this can be really distressing all around. 288 00:14:02,780 --> 00:14:07,120 So it's usually in this moderate stage 289 00:14:07,120 --> 00:14:11,020 that you see families really considering moving somebody 290 00:14:11,020 --> 00:14:14,980 with Alzheimer's from live-in caregiver family situation 291 00:14:14,980 --> 00:14:18,160 into an assisted living sort of nursing home situation, 292 00:14:18,160 --> 00:14:20,950 because the stress and the distress 293 00:14:20,950 --> 00:14:22,750 of handling all of this just being 294 00:14:22,750 --> 00:14:28,090 too much for ordinary people. 295 00:14:28,090 --> 00:14:30,790 And then it progresses into what's 296 00:14:30,790 --> 00:14:32,590 called advanced dementia. 297 00:14:32,590 --> 00:14:37,420 And at this point, all of this just kind of gets worse. 298 00:14:37,420 --> 00:14:42,099 Patients lose motor coordination and muscle tone, 299 00:14:42,099 --> 00:14:44,140 eventually to the point where they are bedridden. 300 00:14:44,140 --> 00:14:45,970 They usually need help feeding themselves. 301 00:14:45,970 --> 00:14:50,980 They usually need help with all kinds of personal care tasks-- 302 00:14:50,980 --> 00:14:53,800 bathing, going to the bathroom, all of this. 303 00:14:53,800 --> 00:14:57,790 They often lose pretty much all linguistic ability 304 00:14:57,790 --> 00:14:58,960 at this point. 305 00:14:58,960 --> 00:15:04,000 And eventually, these patients just lose physical condition 306 00:15:04,000 --> 00:15:07,469 to the extent that any old infection that comes along 307 00:15:07,469 --> 00:15:08,260 will take them out. 308 00:15:08,260 --> 00:15:10,635 And that's usually what people actually die from who have 309 00:15:10,635 --> 00:15:11,650 Alzheimer's. 310 00:15:11,650 --> 00:15:12,850 It's not the disease itself. 311 00:15:12,850 --> 00:15:16,480 It's that the disease leads to this deterioration that 312 00:15:16,480 --> 00:15:18,850 then makes it makes them much more vulnerable 313 00:15:18,850 --> 00:15:21,310 to other kinds of infections. 314 00:15:24,790 --> 00:15:25,790 How long does this take? 315 00:15:25,790 --> 00:15:29,255 Remember it's usually diagnosed that early dementia phase when 316 00:15:29,255 --> 00:15:31,130 you first start seeing significant impairment 317 00:15:31,130 --> 00:15:33,180 in learning and memory. 318 00:15:33,180 --> 00:15:39,260 The mean time for survival after diagnosis is about seven years. 319 00:15:39,260 --> 00:15:41,780 So that's the arithmetical average-- add up all the times 320 00:15:41,780 --> 00:15:44,450 and divides them. 321 00:15:44,450 --> 00:15:48,200 And very few patients, like 3% of patients 322 00:15:48,200 --> 00:15:52,080 alive longer than 14 years after diagnosis. 323 00:15:52,080 --> 00:15:53,520 So this isn't like immediate. 324 00:15:53,520 --> 00:15:58,660 But it's a reasonably quick decline, fade, 325 00:15:58,660 --> 00:16:00,880 death kind of story. 326 00:16:00,880 --> 00:16:02,680 So as you might imagine, lots of people 327 00:16:02,680 --> 00:16:06,610 were trying to figure out what exactly is going on 328 00:16:06,610 --> 00:16:09,110 with Alzheimer's disease. 329 00:16:09,110 --> 00:16:12,550 So what we've known for a while is that there's, macro scale, 330 00:16:12,550 --> 00:16:15,844 pretty substantial differences between normal patients 331 00:16:15,844 --> 00:16:18,010 brains' and the brains of patients with Alzheimer's. 332 00:16:18,010 --> 00:16:19,384 The biggest thing that happens is 333 00:16:19,384 --> 00:16:21,640 that in the temporal and frontal lobes, 334 00:16:21,640 --> 00:16:26,320 you get a lot of cerebral cortex cell death. 335 00:16:26,320 --> 00:16:29,140 Neurons, for one reason or another, 336 00:16:29,140 --> 00:16:32,020 retreat from their synapses with other neurons 337 00:16:32,020 --> 00:16:33,190 and eventually die. 338 00:16:33,190 --> 00:16:35,440 And so what you'll see is that these brains just 339 00:16:35,440 --> 00:16:39,625 have a lot less volume than they do in other-- 340 00:16:39,625 --> 00:16:40,750 so here's a normal patient. 341 00:16:40,750 --> 00:16:43,070 And here's somebody with Alzheimer's disease. 342 00:16:43,070 --> 00:16:46,420 And so you can see the way both the cortex 343 00:16:46,420 --> 00:16:51,017 and all of these subcortical structures have shrunk. 344 00:16:51,017 --> 00:16:52,600 You can see that the ventricle-- which 345 00:16:52,600 --> 00:16:54,474 are the fluid filled spaces that are normally 346 00:16:54,474 --> 00:16:55,900 inside your brain-- have enlarged. 347 00:16:55,900 --> 00:16:58,870 Again, that's the brain itself is taking up less space. 348 00:16:58,870 --> 00:17:02,560 So the cerebral spinal fluid spaces expand. 349 00:17:02,560 --> 00:17:05,560 The hippocampus-- which should be this fit right in here where 350 00:17:05,560 --> 00:17:07,564 it's folded around-- 351 00:17:07,564 --> 00:17:09,980 in a normal patient that would be all the way out to here. 352 00:17:09,980 --> 00:17:11,410 So it's dramatically smaller. 353 00:17:14,829 --> 00:17:18,020 This kind of macro scale, hey look, a lot of cells are dying. 354 00:17:18,020 --> 00:17:20,020 You might imagine, OK, a lot of cells are dying. 355 00:17:20,020 --> 00:17:23,024 It's no wonder that we're seeing this kind of serious cognitive 356 00:17:23,024 --> 00:17:23,524 deficits. 357 00:17:28,986 --> 00:17:30,610 So what's happening on a smaller scale? 358 00:17:30,610 --> 00:17:33,160 Why are cells dying? 359 00:17:33,160 --> 00:17:35,500 So there's two really characteristic changes 360 00:17:35,500 --> 00:17:37,810 that happen at a cellular level in patients 361 00:17:37,810 --> 00:17:39,640 who have Alzheimer's disease. 362 00:17:39,640 --> 00:17:42,470 One of them is what's called these senile plaques, 363 00:17:42,470 --> 00:17:45,190 these beta amyloid plaques. 364 00:17:45,190 --> 00:17:53,380 So what happens is that amyloid precursor protein-- 365 00:17:53,380 --> 00:17:54,430 so this is a neuron. 366 00:17:54,430 --> 00:17:57,310 Here is the cell membrane, here's the interior. 367 00:17:57,310 --> 00:18:00,310 Amyoloid precursor protein is a transmembrane protein. 368 00:18:00,310 --> 00:18:02,750 So it has parts that stick out both into the cell 369 00:18:02,750 --> 00:18:06,010 and out into the extracellular fluid. 370 00:18:06,010 --> 00:18:08,650 We're not entirely sure what it does. 371 00:18:08,650 --> 00:18:13,870 It seems to be important in helping neurons 372 00:18:13,870 --> 00:18:17,620 to grow and to repair themselves after any kind of damage that 373 00:18:17,620 --> 00:18:19,780 might happen to them. 374 00:18:19,780 --> 00:18:24,520 But what happens is that enzymes like 375 00:18:24,520 --> 00:18:28,900 there's one called presenilin. 376 00:18:28,900 --> 00:18:31,540 There's another one who I didn't write down, that was dumb. 377 00:18:31,540 --> 00:18:33,720 But there's a couple of different kinds of enzymes 378 00:18:33,720 --> 00:18:36,580 that, in Alzheimer's patients, seem to go a little bit out 379 00:18:36,580 --> 00:18:37,810 of control. 380 00:18:37,810 --> 00:18:41,020 So they come along, they break up this amyloid precursor 381 00:18:41,020 --> 00:18:43,380 protein into several pieces. 382 00:18:43,380 --> 00:18:46,080 And the piece that's relevant is this bit 383 00:18:46,080 --> 00:18:49,311 that's right here sticking out along the transmembrane part 384 00:18:49,311 --> 00:18:49,810 of it. 385 00:18:49,810 --> 00:18:52,450 This part is called beta-amyloid. 386 00:18:52,450 --> 00:18:54,310 And these beta-amyloid fragments, 387 00:18:54,310 --> 00:18:57,740 when the proteins get snipped up by these enzymes, 388 00:18:57,740 --> 00:18:59,710 float out here in the extracellular fluid. 389 00:18:59,710 --> 00:19:01,450 And they all clump together. 390 00:19:01,450 --> 00:19:05,770 They form these really characteristic senile plaques 391 00:19:05,770 --> 00:19:06,925 or beta-amyloid plaques. 392 00:19:12,290 --> 00:19:16,410 Here's an actual histological slide photo, micrograph. 393 00:19:16,410 --> 00:19:22,970 So you can see in here and here and there, all of these 394 00:19:22,970 --> 00:19:26,180 are places where you've got one of those senile plaques 395 00:19:26,180 --> 00:19:28,240 going on where outside of the cell bodies 396 00:19:28,240 --> 00:19:31,310 there are just all of these bits of beta-amyloid clumped up 397 00:19:31,310 --> 00:19:34,430 on top of each other. 398 00:19:34,430 --> 00:19:37,850 And one theory about what causes the decline 399 00:19:37,850 --> 00:19:40,280 we see in Alzheimer's disease is that these senile 400 00:19:40,280 --> 00:19:45,860 plaques all glom up on top, causing dysfunction 401 00:19:45,860 --> 00:19:47,870 of cellular operation. 402 00:19:47,870 --> 00:19:50,650 But we'll come back to that. 403 00:19:50,650 --> 00:19:51,250 Questions? 404 00:19:54,360 --> 00:19:55,350 Beta-amyloid plaques? 405 00:20:00,550 --> 00:20:05,470 The other big neurological change that you see 406 00:20:05,470 --> 00:20:12,412 is what's called neurofibrillary tangles. 407 00:20:12,412 --> 00:20:13,870 Plaques and tangles, you guys might 408 00:20:13,870 --> 00:20:14,800 have heard about these when you're 409 00:20:14,800 --> 00:20:16,900 reading about Alzheimer's or seeing it discussed. 410 00:20:16,900 --> 00:20:18,980 It's pretty well established at this point. 411 00:20:22,160 --> 00:20:25,420 So what happens here is that these proteins 412 00:20:25,420 --> 00:20:28,850 are part of the cytoskeleton of the neurons. 413 00:20:28,850 --> 00:20:31,090 So you guys probably remember from learning 414 00:20:31,090 --> 00:20:39,511 about cells in bio that cells have a cytoskeleton, which 415 00:20:39,511 --> 00:20:40,510 does a couple of things. 416 00:20:40,510 --> 00:20:43,910 It gives structure to the cell, it helps hold its shape. 417 00:20:43,910 --> 00:20:46,810 But there's also a particular part of the cytoskeleton called 418 00:20:46,810 --> 00:20:48,520 microtubules. 419 00:20:48,520 --> 00:20:52,150 And microtubules act kind of like train 420 00:20:52,150 --> 00:20:54,640 tracks going out to different parts of the cell. 421 00:20:54,640 --> 00:20:59,350 They're involved in transporting proteins and vesicles 422 00:20:59,350 --> 00:21:01,049 of neurotransmitter and other things 423 00:21:01,049 --> 00:21:03,340 that the cell needs to move from one region to another, 424 00:21:03,340 --> 00:21:06,580 it moves along these microtubules. 425 00:21:06,580 --> 00:21:10,060 And one of the things that's involved 426 00:21:10,060 --> 00:21:15,410 in keeping these microtubules stable is these tau proteins. 427 00:21:15,410 --> 00:21:22,280 So diagram moment, so here's our neuron's axon. 428 00:21:22,280 --> 00:21:24,460 And it's got lots of microtubules reaching down, 429 00:21:24,460 --> 00:21:26,920 which are how the cell brings things from its nucleus 430 00:21:26,920 --> 00:21:29,050 out to the axon tips. 431 00:21:29,050 --> 00:21:34,660 And normally, these tau proteins have a phosphate group on them, 432 00:21:34,660 --> 00:21:37,090 they're phosphorylated. 433 00:21:37,090 --> 00:21:41,800 And at that point, the presence of a phosphate group 434 00:21:41,800 --> 00:21:44,290 causes them to fold in such a shape 435 00:21:44,290 --> 00:21:45,970 that they stabilize the microtubule. 436 00:21:45,970 --> 00:21:48,730 They help hold it all together. 437 00:21:48,730 --> 00:21:51,280 And what happens in patients with Alzheimer's disease 438 00:21:51,280 --> 00:21:54,100 is that these tau proteins that should 439 00:21:54,100 --> 00:21:56,680 be holding the microtubule together 440 00:21:56,680 --> 00:21:58,470 become hyper-phosphorylated. 441 00:21:58,470 --> 00:22:01,120 They get extra phosphate groups stuck onto them-- 442 00:22:01,120 --> 00:22:02,800 --That makes them unstable-- 443 00:22:02,800 --> 00:22:04,000 --which makes them unstable. 444 00:22:04,000 --> 00:22:08,080 It causes them to change shape because proteins 445 00:22:08,080 --> 00:22:09,672 are made up of amino acids. 446 00:22:09,672 --> 00:22:11,380 and they want to fold up in such a manner 447 00:22:11,380 --> 00:22:14,782 that the electric charges are all attracted and pushing apart 448 00:22:14,782 --> 00:22:15,490 in the right way. 449 00:22:18,500 --> 00:22:21,760 And so as you start adding phosphate groups onto them, 450 00:22:21,760 --> 00:22:24,970 we talked about how phospholating receptors-- 451 00:22:24,970 --> 00:22:27,040 we talked two weeks ago about this-- 452 00:22:27,040 --> 00:22:28,720 causes them to change their behavior. 453 00:22:28,720 --> 00:22:31,931 Again, it's a subtle change in shape that makes this happen. 454 00:22:31,931 --> 00:22:34,180 So in this case when you stick to any phosphate groups 455 00:22:34,180 --> 00:22:37,150 on a tau protein, it shifts. 456 00:22:37,150 --> 00:22:40,440 It no longer manages to hold the microtubule together. 457 00:22:40,440 --> 00:22:42,970 And so what happens is that this microtubule 458 00:22:42,970 --> 00:22:45,040 starts to fall apart. 459 00:22:45,040 --> 00:22:47,560 And the tau proteins, again, all clump together 460 00:22:47,560 --> 00:22:53,946 and wrap around each other in these neurofibrillary tangles. 461 00:22:53,946 --> 00:22:57,292 AUDIENCE: Can you go back one? 462 00:22:57,292 --> 00:22:58,250 ABBY NOYCE: Maybe, yes. 463 00:23:16,832 --> 00:23:21,156 AUDIENCE: So the two cellular level 464 00:23:21,156 --> 00:23:24,680 sequences that we looked at, are these causes of the cell 465 00:23:24,680 --> 00:23:26,355 deaths? 466 00:23:26,355 --> 00:23:28,480 ABBY NOYCE: Nobody is entirely sure how that works. 467 00:23:28,480 --> 00:23:30,250 There's hypotheses that say that these are 468 00:23:30,250 --> 00:23:32,200 the causes of the cell deaths. 469 00:23:32,200 --> 00:23:35,470 What we know is that they're distinct. 470 00:23:35,470 --> 00:23:38,380 They happen in normal aging too, but they happen much more 471 00:23:38,380 --> 00:23:41,710 in Alzheimer's patients and in different parts of the brain. 472 00:23:41,710 --> 00:23:44,380 And so it's traditionally looking 473 00:23:44,380 --> 00:23:47,770 at these particular cellular level 474 00:23:47,770 --> 00:23:50,470 changes has been how that definitive Alzheimer's 475 00:23:50,470 --> 00:23:52,117 diagnosis is made. 476 00:23:52,117 --> 00:23:54,200 You say, OK, you've got all the clinical symptoms. 477 00:23:54,200 --> 00:23:55,990 And after somebody dies, you do an autopsy. 478 00:23:55,990 --> 00:23:58,115 You take a slice of their brain, and you look at it 479 00:23:58,115 --> 00:24:03,304 under a microscope for the tangles and for the plaques. 480 00:24:03,304 --> 00:24:04,720 They're starting to be some better 481 00:24:04,720 --> 00:24:06,760 ways of doing this and some better ways 482 00:24:06,760 --> 00:24:10,400 of on non-autopsy required diagnoses. 483 00:24:10,400 --> 00:24:12,400 But so we've got-- 484 00:24:12,400 --> 00:24:14,574 AUDIENCE: Does that mean Alzheimer's can only 485 00:24:14,574 --> 00:24:18,930 be diagnosed after death? 486 00:24:18,930 --> 00:24:20,340 ABBY NOYCE: Definitively, yes. 487 00:24:20,340 --> 00:24:22,830 That is likely to change in the next five or 10 years, 488 00:24:22,830 --> 00:24:23,580 I suspect. 489 00:24:23,580 --> 00:24:28,050 Or at least our non-death requiring diagnosis methods 490 00:24:28,050 --> 00:24:28,800 will get better. 491 00:24:32,172 --> 00:24:34,380 So one of the things that happens with Alzheimer's is 492 00:24:34,380 --> 00:24:36,880 you see tissue loss and distinctive parts of the brain. 493 00:24:36,880 --> 00:24:38,262 You see it in the hippocampus. 494 00:24:38,262 --> 00:24:39,720 You see it in the prefrontal lobes. 495 00:24:39,720 --> 00:24:42,599 You see it in particular regions of the temporal lobes. 496 00:24:42,599 --> 00:24:44,140 You see it along the cingulate gyrus, 497 00:24:44,140 --> 00:24:46,015 which is that part of the frontal lobes where 498 00:24:46,015 --> 00:24:49,260 they nudge up against each other in the middle. 499 00:24:49,260 --> 00:24:51,240 And you can pick out some of that 500 00:24:51,240 --> 00:24:54,350 on an on neuroimaging system like an MRI 501 00:24:54,350 --> 00:24:55,950 as the resolution on MRI gets better. 502 00:24:58,890 --> 00:25:01,274 There's a staining technique-- 503 00:25:01,274 --> 00:25:03,690 well, not quite a staining technique, an imaging technique 504 00:25:03,690 --> 00:25:05,070 that works like PET. 505 00:25:05,070 --> 00:25:08,250 Remember in classic PET scans where 506 00:25:08,250 --> 00:25:11,040 you're looking at what parts of the brain are active, 507 00:25:11,040 --> 00:25:13,050 people would drink this radioactive glucose. 508 00:25:13,050 --> 00:25:14,880 And then you'd scan where the radioactivity 509 00:25:14,880 --> 00:25:17,489 was emitted from because it would get picked up 510 00:25:17,489 --> 00:25:18,030 in the blood. 511 00:25:18,030 --> 00:25:19,440 And then it would be sent to the parts of the brain that 512 00:25:19,440 --> 00:25:21,150 were working the hardest. 513 00:25:21,150 --> 00:25:25,230 Somebody has done a modification of that where you have patients 514 00:25:25,230 --> 00:25:32,520 drink a substance that has a radioactive molecule that 515 00:25:32,520 --> 00:25:37,410 will bind to, not to the tau proteins, but to the flax, 516 00:25:37,410 --> 00:25:40,000 to these beta-amyloid fragments. 517 00:25:40,000 --> 00:25:44,310 And so if you have a molecule that will bind specifically 518 00:25:44,310 --> 00:25:47,190 to that and then you can stick a radioactive tracer 519 00:25:47,190 --> 00:25:49,950 onto that molecule and you have this then bind 520 00:25:49,950 --> 00:25:54,542 to these plaques, you can see how much of it 521 00:25:54,542 --> 00:25:55,500 is in somebody's brain. 522 00:25:55,500 --> 00:25:56,880 You can measure the level of it which sticks. 523 00:25:56,880 --> 00:25:59,580 And you can look at the distribution of these plaques. 524 00:25:59,580 --> 00:26:01,590 And there are people working to figure out 525 00:26:01,590 --> 00:26:04,860 what the exact criteria for a diagnosis using this would be. 526 00:26:04,860 --> 00:26:08,244 So like I said, there's better diagnosis tools 527 00:26:08,244 --> 00:26:09,660 kind of in the pipeline right now. 528 00:26:12,115 --> 00:26:13,990 But you know, some people don't want to know. 529 00:26:13,990 --> 00:26:15,840 That's the other half of it is some people 530 00:26:15,840 --> 00:26:18,419 will say no, I'm not going to get tested for this. 531 00:26:18,419 --> 00:26:19,960 I'm not going to get screened for it. 532 00:26:19,960 --> 00:26:21,418 If I'm going to die in seven years, 533 00:26:21,418 --> 00:26:23,742 I don't want to know about it. 534 00:26:23,742 --> 00:26:24,325 AUDIENCE: Why? 535 00:26:28,070 --> 00:26:30,630 ABBY NOYCE: Many people-- 536 00:26:30,630 --> 00:26:33,050 this is something that keeps coming up, especially-- 537 00:26:36,709 --> 00:26:38,000 Yeah, some people want to know. 538 00:26:38,000 --> 00:26:38,916 And some people don't. 539 00:26:38,916 --> 00:26:40,375 So there's a lot of things like I 540 00:26:40,375 --> 00:26:41,750 don't know if you guys have heard 541 00:26:41,750 --> 00:26:44,510 of Huntington's disease, which is 542 00:26:44,510 --> 00:26:48,710 a neurodegenerative disease that usually first kicks in 543 00:26:48,710 --> 00:26:49,970 around age 45. 544 00:26:49,970 --> 00:26:52,110 It's also heritable. 545 00:26:52,110 --> 00:26:54,350 So one of the things that tends to happen 546 00:26:54,350 --> 00:26:58,346 is people happily have kids in their 20s and 30s. 547 00:26:58,346 --> 00:26:59,720 And then they hit 45 and find out 548 00:26:59,720 --> 00:27:02,651 that they have Huntington's and then realize that they have 549 00:27:02,651 --> 00:27:04,150 probably passed it to their children 550 00:27:04,150 --> 00:27:06,830 go, oh no, I didn't know that, whatever. 551 00:27:06,830 --> 00:27:11,420 And so Huntington's is one of the easy to find, 552 00:27:11,420 --> 00:27:13,610 easy to genetically test for diseases. 553 00:27:13,610 --> 00:27:16,414 It's a mutation on one gene, on one chromosome. 554 00:27:16,414 --> 00:27:18,830 There is one very small chance that we can look at and say 555 00:27:18,830 --> 00:27:21,710 this is the thing that causes Huntington's. 556 00:27:21,710 --> 00:27:23,226 So now you can get tested for it. 557 00:27:23,226 --> 00:27:25,100 You can give a drop of blood through the lab, 558 00:27:25,100 --> 00:27:27,830 and they'll run a screen and they'll test for it. 559 00:27:27,830 --> 00:27:29,630 And some people want to know. 560 00:27:29,630 --> 00:27:31,160 And some people absolutely don't. 561 00:27:31,160 --> 00:27:33,118 They know they have a parent who had it so they 562 00:27:33,118 --> 00:27:35,101 have a 50% chance of having it. 563 00:27:35,101 --> 00:27:37,100 And they do not want to know yes or no for sure. 564 00:27:37,100 --> 00:27:40,250 And you can't require them to get tested or anything. 565 00:27:40,250 --> 00:27:42,410 But this sort of testing starts bringing up 566 00:27:42,410 --> 00:27:43,490 all sorts of issues. 567 00:27:43,490 --> 00:27:46,762 As we get and as we get more and more ideas 568 00:27:46,762 --> 00:27:49,220 about what the genetic bases of different kinds of diseases 569 00:27:49,220 --> 00:27:52,809 are, we're going to see these issues come up more and more. 570 00:27:52,809 --> 00:27:53,350 I don't know. 571 00:27:53,350 --> 00:27:56,090 I was listening to NPR this afternoon in the car. 572 00:27:56,090 --> 00:27:58,930 And they were talking about HIV testing and again 573 00:27:58,930 --> 00:27:59,720 the same thing. 574 00:27:59,720 --> 00:28:01,200 Lots of people don't want to know. 575 00:28:01,200 --> 00:28:02,450 They don't want to get tested. 576 00:28:02,450 --> 00:28:06,640 They don't want to know for an assortment of reasons. 577 00:28:06,640 --> 00:28:08,670 It's an interesting question. 578 00:28:08,670 --> 00:28:11,252 It's a difficult question And some of those cases 579 00:28:11,252 --> 00:28:13,460 where you might know for sure what the answer for you 580 00:28:13,460 --> 00:28:16,670 is but it's very hard to say that the answer for everybody 581 00:28:16,670 --> 00:28:17,670 should be this or that. 582 00:28:21,850 --> 00:28:26,230 So we that these two kinds of cellular molecular changes that 583 00:28:26,230 --> 00:28:32,650 you see in the brains of patients who have Alzheimer's. 584 00:28:32,650 --> 00:28:36,020 So here's again a micrograph of a neurofibrillary tangles 585 00:28:36,020 --> 00:28:38,860 you can see the different strands in here that are all 586 00:28:38,860 --> 00:28:41,289 wrapped around each other. 587 00:28:41,289 --> 00:28:43,330 They make this kind of characteristic flame shape 588 00:28:43,330 --> 00:28:47,332 that you can see in different kinds of staining. 589 00:28:47,332 --> 00:28:50,800 AUDIENCE: It always looks like that? 590 00:28:50,800 --> 00:28:52,750 ABBY NOYCE: It's not always quite that pretty. 591 00:28:52,750 --> 00:28:54,791 But I mean, if you look at this photo micrograph. 592 00:28:54,791 --> 00:28:57,520 So this photo micrograph claims to only 593 00:28:57,520 --> 00:29:00,100 be showing the senile plaques. 594 00:29:00,100 --> 00:29:02,890 But all of these shapes in here-- 595 00:29:02,890 --> 00:29:04,960 see these? 596 00:29:04,960 --> 00:29:09,165 I am not a trained cyto-histological person 597 00:29:09,165 --> 00:29:11,290 in identifying Alzheimer's disease characteristics. 598 00:29:11,290 --> 00:29:15,150 But those look very similar to me, in my untrained state, 599 00:29:15,150 --> 00:29:17,884 to photo micrograph I've seen of what 600 00:29:17,884 --> 00:29:19,300 these neurofibrillary tangles look 601 00:29:19,300 --> 00:29:22,150 like that discussed that characteristic flame shape. 602 00:29:22,150 --> 00:29:24,319 So I looked at this and said, you're not 603 00:29:24,319 --> 00:29:25,610 telling me that's what's there. 604 00:29:25,610 --> 00:29:27,530 But I wonder if these are what they are. 605 00:29:27,530 --> 00:29:28,420 So I don't know. 606 00:29:28,420 --> 00:29:31,904 But they do tend to always have this very characteristic shape 607 00:29:31,904 --> 00:29:34,070 where they are narrow on one end and kind of rounder 608 00:29:34,070 --> 00:29:36,770 on the other. 609 00:29:36,770 --> 00:29:38,620 AUDIENCE: And that's just how they form? 610 00:29:38,620 --> 00:29:40,210 ABBY NOYCE: That's just how they form. 611 00:29:40,210 --> 00:29:41,777 remember this is caused by proteins 612 00:29:41,777 --> 00:29:43,610 wrapping around each other in a certain way. 613 00:29:43,610 --> 00:29:44,620 So there's going to be characteristics 614 00:29:44,620 --> 00:29:46,745 of how the charge is on different parts of them are 615 00:29:46,745 --> 00:29:49,420 what's attracted and what's repelled that causes 616 00:29:49,420 --> 00:29:51,076 particular deformations. 617 00:29:54,730 --> 00:29:56,670 So like I said, these are things that you see 618 00:29:56,670 --> 00:29:58,069 in patients with normal aging. 619 00:29:58,069 --> 00:30:00,110 But there's more of them in Alzheimer's patients. 620 00:30:00,110 --> 00:30:02,610 They're distributed differently. 621 00:30:02,610 --> 00:30:04,950 There's kind of an ongoing theoretical argument 622 00:30:04,950 --> 00:30:09,120 about whether Alzheimer's is just normal aging happening 623 00:30:09,120 --> 00:30:11,490 worse in some patients or if it's actually 624 00:30:11,490 --> 00:30:16,950 something that is qualitatively different than normal aging. 625 00:30:16,950 --> 00:30:18,660 And oh hey, terminology moment. 626 00:30:18,660 --> 00:30:21,630 So Alzheimer's is a proteopathy-- 627 00:30:21,630 --> 00:30:24,330 which is a word I hadn't heard before actually-- 628 00:30:24,330 --> 00:30:27,060 which refers to diseases that happen because of a protein 629 00:30:27,060 --> 00:30:28,210 misfolding. 630 00:30:28,210 --> 00:30:28,710 Issue. 631 00:30:28,710 --> 00:30:32,170 So proteins fold up into a particular shape. 632 00:30:32,170 --> 00:30:34,500 And it's that shape which gives them their function. 633 00:30:34,500 --> 00:30:37,250 Think again about ion channels in the cell, 634 00:30:37,250 --> 00:30:39,780 they've got to have those different subcomponents lined 635 00:30:39,780 --> 00:30:43,990 up in a little cylinder in order to ions in and out. 636 00:30:43,990 --> 00:30:45,660 Of shape is important for proteins. 637 00:30:45,660 --> 00:30:49,060 When proteins go wrong, they can't do their job anymore. 638 00:30:52,680 --> 00:30:53,917 So what causes this? 639 00:30:53,917 --> 00:30:56,250 There's a couple of hypotheses about what the underlying 640 00:30:56,250 --> 00:30:58,560 causes are of Alzheimer's disease. 641 00:30:58,560 --> 00:31:01,380 One of the things we know is that early stage 642 00:31:01,380 --> 00:31:05,640 Alzheimer's tends to involve particularly the damage 643 00:31:05,640 --> 00:31:09,610 to the basal forebrain cholingeric system. 644 00:31:09,610 --> 00:31:14,730 So you guys all remember this is subcortical mostly 645 00:31:14,730 --> 00:31:18,690 kind of towards the frontal lobe subcortical structures where 646 00:31:18,690 --> 00:31:20,520 most of the acetylcholine in your brain 647 00:31:20,520 --> 00:31:23,700 comes from, its cells who have their cell bodies in this area 648 00:31:23,700 --> 00:31:27,012 and then project them through almost all of cortex. 649 00:31:27,012 --> 00:31:28,470 And one thing we know is that these 650 00:31:28,470 --> 00:31:31,650 are one of the first cells to deteriorate and start 651 00:31:31,650 --> 00:31:33,210 to die in Alzheimer's disease. 652 00:31:35,740 --> 00:31:39,680 And one of the oldest hypotheses is that this reduced synthesis 653 00:31:39,680 --> 00:31:45,940 of acetylcholine is the thing that causes Alzheimer's. 654 00:31:45,940 --> 00:31:49,260 There are four medications for Alzheimer's on the market 655 00:31:49,260 --> 00:31:54,450 right now That are approved by the FDA and so on. 656 00:31:54,450 --> 00:31:58,140 Three of them all work on acetylcholine. 657 00:31:58,140 --> 00:32:00,150 They all are acetylcholinesterase 658 00:32:00,150 --> 00:32:01,990 inhibitors. 659 00:32:01,990 --> 00:32:04,350 Acetylcholinesterase is the enzyme 660 00:32:04,350 --> 00:32:07,620 that cleans up acetylcholine out of the synapse 661 00:32:07,620 --> 00:32:09,660 after it's been released by a pre-synpatic cell. 662 00:32:12,870 --> 00:32:15,554 So if you inhibit acetylcholinesterase then 663 00:32:15,554 --> 00:32:17,970 what's going to happen is that every time acetylcholine is 664 00:32:17,970 --> 00:32:19,680 released into the synapse, it's going 665 00:32:19,680 --> 00:32:20,950 to hang around for longer. 666 00:32:20,950 --> 00:32:22,561 It's not to get cleaned up so quickly. 667 00:32:22,561 --> 00:32:24,060 And so at least to some extent, this 668 00:32:24,060 --> 00:32:26,550 can make up for a reduced amount of it being released. 669 00:32:26,550 --> 00:32:31,110 Because it gets to stay around longer, it evens out 670 00:32:31,110 --> 00:32:33,480 It's kind of the same logic as SSRIs 671 00:32:33,480 --> 00:32:38,430 selective serotonin reuptake inhibitors as antidepressants. 672 00:32:38,430 --> 00:32:41,740 If we inhibit the re-uptake of serotonin, 673 00:32:41,740 --> 00:32:43,560 let it sit in the synapse longer, 674 00:32:43,560 --> 00:32:46,830 than it'll make up for a decreased amount of serotonin 675 00:32:46,830 --> 00:32:48,270 being released. 676 00:32:48,270 --> 00:32:50,550 So in this case, we're looking at acetylcholine 677 00:32:50,550 --> 00:32:54,730 from this basal forebrain cholingeric system. 678 00:32:54,730 --> 00:32:59,550 So these acetylcholinesterase inhibitors 679 00:32:59,550 --> 00:33:01,690 work reasonably well. 680 00:33:01,690 --> 00:33:05,800 They definitely have an effect on the symptoms of early stage 681 00:33:05,800 --> 00:33:06,300 Alzheimer's. 682 00:33:06,300 --> 00:33:08,220 They help people who are having memory impairment. 683 00:33:08,220 --> 00:33:09,095 They'll improve that. 684 00:33:09,095 --> 00:33:10,830 They'll improve cognitive function. 685 00:33:10,830 --> 00:33:13,110 It's not huge, but it's definitely an improvement. 686 00:33:13,110 --> 00:33:15,050 That's why they're on the market. 687 00:33:15,050 --> 00:33:16,800 But they don't stop it from getting worse. 688 00:33:16,800 --> 00:33:19,830 It's like this is a Band-Aid sort of solution. 689 00:33:19,830 --> 00:33:22,950 It also really doesn't seem to make any difference 690 00:33:22,950 --> 00:33:24,870 as the dementia progresses as it gets worse. 691 00:33:29,520 --> 00:33:32,590 They stop having really any measurable effect at all. 692 00:33:32,590 --> 00:33:34,290 So this is an early stage treatment. 693 00:33:34,290 --> 00:33:39,270 It treats the symptoms, doesn't stop things from getting worse. 694 00:33:39,270 --> 00:33:41,310 The other medication that's on the market right 695 00:33:41,310 --> 00:33:45,300 now is based on a different idea. 696 00:33:45,300 --> 00:33:47,570 You guys remember we talked about glutamate 697 00:33:47,570 --> 00:33:50,160 when we were talking about long term potentiation in learning 698 00:33:50,160 --> 00:33:51,430 and memory? 699 00:33:51,430 --> 00:33:53,790 So one of the things that happens 700 00:33:53,790 --> 00:33:56,610 that glutamatergic cells have to watch out for 701 00:33:56,610 --> 00:33:59,700 is that if a cell takes up too much glutamate, 702 00:33:59,700 --> 00:34:01,650 it actually will die. 703 00:34:01,650 --> 00:34:03,169 It's called excitotoxicity. 704 00:34:03,169 --> 00:34:04,710 If there's too much glutamate release 705 00:34:04,710 --> 00:34:07,210 into a certain region of the brain, 706 00:34:07,210 --> 00:34:09,719 it will actually kill those cells. 707 00:34:09,719 --> 00:34:11,894 Not sure exactly how this happens. 708 00:34:11,894 --> 00:34:13,560 We're not sure exactly how this happens. 709 00:34:13,560 --> 00:34:15,630 It may have to do with too much calcium coming 710 00:34:15,630 --> 00:34:20,219 in through those NMDA receptors that can let in calcium. 711 00:34:20,219 --> 00:34:24,090 And then the calcium triggers apoptosis which is that 712 00:34:24,090 --> 00:34:26,190 and then the cell basically commit suicide. 713 00:34:26,190 --> 00:34:28,170 The cell says, oops, something is very wrong. 714 00:34:28,170 --> 00:34:31,150 I'm going to kill myself now, shut down, disintegrate. 715 00:34:31,150 --> 00:34:33,659 So apoptosis-- you guys probably remember from bio-- 716 00:34:33,659 --> 00:34:36,219 is that programmed cell death. 717 00:34:36,219 --> 00:34:38,219 Cell death where they get some kind of signal 718 00:34:38,219 --> 00:34:40,260 from his surroundings that it is no longer 719 00:34:40,260 --> 00:34:42,330 needed, and it should wrap up its business 720 00:34:42,330 --> 00:34:44,820 as nearly as possible and disintegrate. 721 00:34:44,820 --> 00:34:47,610 So the other Alzheimer's disease medication 722 00:34:47,610 --> 00:34:53,820 is trying to combat this excitotoxicity problem 723 00:34:53,820 --> 00:34:56,400 by working on NMDA receptors. 724 00:34:56,400 --> 00:34:59,340 It's an antagonist for NMDA receptors. 725 00:34:59,340 --> 00:35:03,300 So it sticks to the same spot that glutamate does. 726 00:35:03,300 --> 00:35:04,720 It reacts to the glutamate binding 727 00:35:04,720 --> 00:35:06,870 site on the NMDA receptor. 728 00:35:06,870 --> 00:35:08,970 But instead of opening the receptor channel 729 00:35:08,970 --> 00:35:12,240 the way glutamate does, it just kind of sits there 730 00:35:12,240 --> 00:35:12,840 and blocks it. 731 00:35:12,840 --> 00:35:15,557 So it's not the right shape to trigger it to open. 732 00:35:15,557 --> 00:35:17,640 And it's in the way so the glutamate can't come in 733 00:35:17,640 --> 00:35:18,890 and trigger it to open either. 734 00:35:18,890 --> 00:35:24,870 So again, this medication reduces 735 00:35:24,870 --> 00:35:28,620 that excitotoxocity, but much like these cholinergic 736 00:35:28,620 --> 00:35:31,290 medications, doesn't seem to stop long term 737 00:35:31,290 --> 00:35:34,260 prediction of the disease. 738 00:35:34,260 --> 00:35:36,630 It treats symptoms, and treat symptoms 739 00:35:36,630 --> 00:35:38,790 later then the cholinergic drugs do. 740 00:35:38,790 --> 00:35:41,800 The cholingeric drugs treat early dementia. 741 00:35:41,800 --> 00:35:44,970 The glutamateric drugs seems to reduce symptoms of mid 742 00:35:44,970 --> 00:35:45,930 to late stage dementia. 743 00:35:45,930 --> 00:35:48,009 But again, it doesn't stop the progression. 744 00:35:48,009 --> 00:35:49,425 AUDIENCE: So what effect does that 745 00:35:49,425 --> 00:35:51,477 have on the person if they don't have glutamate 746 00:35:51,477 --> 00:35:52,560 getting into their system? 747 00:35:52,560 --> 00:35:55,059 ABBY NOYCE: So it's not going to block all of the glutamate. 748 00:35:55,059 --> 00:35:57,870 And it's only going to work on the NMDA receptors. 749 00:35:57,870 --> 00:36:00,420 Actually, the side effects for this one are moderately mild. 750 00:36:00,420 --> 00:36:04,410 The side effects are things like slight dizziness and headaches. 751 00:36:04,410 --> 00:36:06,600 Whereas the acetylcholinesterase drugs actually 752 00:36:06,600 --> 00:36:08,850 have some really nasty side effects or they can. 753 00:36:08,850 --> 00:36:11,340 They're kind of rare, because they see the calling is also 754 00:36:11,340 --> 00:36:14,966 the neurotransmitter that's used at the neuromuscular junction. 755 00:36:14,966 --> 00:36:16,590 So if you mess up acetylcholinesterase, 756 00:36:16,590 --> 00:36:18,480 you're also messing up what happens everywhere 757 00:36:18,480 --> 00:36:19,896 your nervous system tells a muscle 758 00:36:19,896 --> 00:36:21,688 to do something, which is your entire body. 759 00:36:21,688 --> 00:36:23,979 And you can get some really weird side effects going on 760 00:36:23,979 --> 00:36:24,570 with those. 761 00:36:30,180 --> 00:36:32,190 A lot of these drugs can have weird side effects 762 00:36:32,190 --> 00:36:35,130 because they aren't as precisely targeted as one might like, 763 00:36:35,130 --> 00:36:37,539 especially for something like Alzheimer's, which affects, 764 00:36:37,539 --> 00:36:40,080 especially in its later stages, pretty much the entire brain. 765 00:36:44,137 --> 00:36:45,720 So this is the cholinergic hypothesis. 766 00:36:45,720 --> 00:36:47,430 This has pretty much gone out of favor, 767 00:36:47,430 --> 00:36:50,204 because you can fix the amount of acetylcholine that's 768 00:36:50,204 --> 00:36:51,870 in the brain, at least for early stages. 769 00:36:51,870 --> 00:36:55,210 But it doesn't actually change how the disease progresses. 770 00:36:55,210 --> 00:36:57,450 So at this point, the reduced amount of acetylcholine 771 00:36:57,450 --> 00:37:00,090 seems to be a symptom of the disease 772 00:37:00,090 --> 00:37:02,170 but not a cause of the disease itself. 773 00:37:02,170 --> 00:37:05,040 So the disease is eating the basal forebrain 774 00:37:05,040 --> 00:37:08,310 cholinergic cells, which then causes 775 00:37:08,310 --> 00:37:10,430 acetylcholine to be reduced. 776 00:37:10,430 --> 00:37:12,350 All right. 777 00:37:12,350 --> 00:37:16,250 So the other is kind of two main causes that are discussed 778 00:37:16,250 --> 00:37:18,770 is that it's either these tau proteins 779 00:37:18,770 --> 00:37:23,360 or these amyloid protein masses that are causing 780 00:37:23,360 --> 00:37:26,090 some amount of cell toxicity. 781 00:37:26,090 --> 00:37:30,590 So the tau hypothesis says that what's happening 782 00:37:30,590 --> 00:37:33,620 is that these tau proteins, for whatever reason, 783 00:37:33,620 --> 00:37:35,000 become hyper-phosphorylated. 784 00:37:35,000 --> 00:37:36,650 They change shape. 785 00:37:36,650 --> 00:37:41,060 The microtubules that they were holding together fall apart. 786 00:37:41,060 --> 00:37:43,580 And when the cell can no longer transport things 787 00:37:43,580 --> 00:37:46,580 down the microtubules to the tips of its axons, 788 00:37:46,580 --> 00:37:51,260 then its ability to communicate with other cells fails. 789 00:37:51,260 --> 00:37:53,420 So first of all, you're seeing these decreases 790 00:37:53,420 --> 00:37:57,469 in cognition that can just be explained by synapses breaking, 791 00:37:57,469 --> 00:37:59,510 down by cells no longer being able to communicate 792 00:37:59,510 --> 00:38:01,040 across synapses. 793 00:38:01,040 --> 00:38:03,840 And over time as the cytoskeleton disintegrates 794 00:38:03,840 --> 00:38:07,303 further, you're going to get apoptosis and programmed cell 795 00:38:07,303 --> 00:38:08,210 death. 796 00:38:08,210 --> 00:38:10,251 So there's just one theory. 797 00:38:10,251 --> 00:38:11,750 There are some researchers who think 798 00:38:11,750 --> 00:38:12,958 that this is what's going on. 799 00:38:12,958 --> 00:38:14,870 There is research being done into it. 800 00:38:14,870 --> 00:38:16,940 But most researchers who are studying 801 00:38:16,940 --> 00:38:19,700 this stuff think that's what's going on 802 00:38:19,700 --> 00:38:22,730 is in this amyloid stuff. 803 00:38:22,730 --> 00:38:27,290 And there's a couple of good theories for this. 804 00:38:27,290 --> 00:38:32,090 So one hypothesis is that these amyloid plaques, 805 00:38:32,090 --> 00:38:35,210 by breaking up the amyloid precursor proteins, that 806 00:38:35,210 --> 00:38:38,960 transmembrane proteins and forming these amyloid plaques 807 00:38:38,960 --> 00:38:46,520 in the extracellular fluid, then this in turn 808 00:38:46,520 --> 00:38:49,590 messes up the calcium balance in the cell. 809 00:38:49,590 --> 00:38:52,529 So the cells have to have a precise amount of calcium. 810 00:38:52,529 --> 00:38:54,320 If they have too little, bad stuff happens. 811 00:38:54,320 --> 00:38:56,750 If they have too much, bad stuff happens. 812 00:38:56,750 --> 00:38:58,370 And it's the presence of these plaques 813 00:38:58,370 --> 00:39:02,480 that causes these cells that have too much calcium inside. 814 00:39:02,480 --> 00:39:06,830 Their calcium homeostasis mechanisms get broken. 815 00:39:06,830 --> 00:39:08,900 Too much calcium, as we discussed a minute ago 816 00:39:08,900 --> 00:39:12,530 with toxicity, can then lead to apoptosis, 817 00:39:12,530 --> 00:39:15,170 to this programmed cell death idea. 818 00:39:15,170 --> 00:39:16,970 These are explanations in particular 819 00:39:16,970 --> 00:39:19,770 not just for the symptoms of Alzheimer's disease, 820 00:39:19,770 --> 00:39:22,310 but for the very specific dramatic cell death 821 00:39:22,310 --> 00:39:24,200 that you see as this disease progresses. 822 00:39:26,870 --> 00:39:30,530 One of the most interesting pieces 823 00:39:30,530 --> 00:39:33,620 of evidence in favor of this amyloid hypothesis 824 00:39:33,620 --> 00:39:36,500 is that that amyloid precursor protein-- remember 825 00:39:36,500 --> 00:39:39,740 that's the big transmembrane protein that gets broken up 826 00:39:39,740 --> 00:39:43,820 to form the amyloid beta that then forms the senile plaques. 827 00:39:43,820 --> 00:39:49,190 So this amyloid precursor protein is on chromosome 21. 828 00:39:49,190 --> 00:39:53,480 And as you guys probably know, trisomy, 829 00:39:53,480 --> 00:39:56,870 if you have three copies of chromosome 21, 830 00:39:56,870 --> 00:39:58,899 you get down syndrome. 831 00:39:58,899 --> 00:40:00,690 Anyone here know anyone with Down syndrome? 832 00:40:00,690 --> 00:40:03,189 There was a kid in my class at school who had down syndrome. 833 00:40:05,920 --> 00:40:08,860 So down syndrome patients have a really characteristic 834 00:40:08,860 --> 00:40:09,490 facial shape. 835 00:40:09,490 --> 00:40:14,530 They tend to have poor vision, poor hearing, low IQs, 836 00:40:14,530 --> 00:40:16,426 all of that. 837 00:40:16,426 --> 00:40:17,800 And the thing about down syndrome 838 00:40:17,800 --> 00:40:21,250 is that down syndrome patients almost always 839 00:40:21,250 --> 00:40:23,500 exhibit symptoms that are very much like those 840 00:40:23,500 --> 00:40:25,000 of Alzheimer's disease. 841 00:40:25,000 --> 00:40:26,170 And they get this early. 842 00:40:26,170 --> 00:40:28,810 They don't get this at 65 or 75 or 85. 843 00:40:28,810 --> 00:40:34,030 Down syndrome patients get this in their late 30s. 844 00:40:34,030 --> 00:40:37,470 They start showing impaired learning, impaired memory, 845 00:40:37,470 --> 00:40:39,940 not just relative to normal IQ people, 846 00:40:39,940 --> 00:40:42,310 but relative to where they were previously. 847 00:40:42,310 --> 00:40:44,560 And it follows pretty much all of the same progression 848 00:40:44,560 --> 00:40:47,860 patterns as Alzheimer's disease does. 849 00:40:47,860 --> 00:40:53,920 And the fact that the chromosome that's involved down syndrome 850 00:40:53,920 --> 00:40:55,930 is the chromosome that has the gene 851 00:40:55,930 --> 00:40:59,080 for this hypothesized cause is a kind 852 00:40:59,080 --> 00:41:01,894 of promising piece of evidence. 853 00:41:01,894 --> 00:41:03,310 And it makes some amount of sense. 854 00:41:03,310 --> 00:41:05,660 These things seem to be related. 855 00:41:05,660 --> 00:41:12,790 Another piece of evidence in favor of the amyloid hypothesis 856 00:41:12,790 --> 00:41:17,140 is that Alzheimer's disease is, at least to some extent, 857 00:41:17,140 --> 00:41:18,490 a heritable disease. 858 00:41:18,490 --> 00:41:20,649 There's a genetic component to it. 859 00:41:20,649 --> 00:41:22,690 And there's a couple of different heritable types 860 00:41:22,690 --> 00:41:24,189 of Alzheimer's that have been traced 861 00:41:24,189 --> 00:41:26,620 to a couple of different genes. 862 00:41:26,620 --> 00:41:29,110 One is a mutation on the gene that produces 863 00:41:29,110 --> 00:41:32,020 this amyloid precursor protein. 864 00:41:32,020 --> 00:41:35,440 There's also a couple of what are called these presenilins, 865 00:41:35,440 --> 00:41:37,900 these enzymes that break up the amyloid precursor 866 00:41:37,900 --> 00:41:40,840 protein to form the beta plaques, 867 00:41:40,840 --> 00:41:42,760 the amyloid-beta plaques. 868 00:41:42,760 --> 00:41:44,960 And mutations for a different form of presenilins 869 00:41:44,960 --> 00:41:48,970 are another heritable form of Alzheimer's, another place 870 00:41:48,970 --> 00:41:51,170 where it's been traced to a particular gene. 871 00:41:51,170 --> 00:41:55,420 So both of these pieces have a genetic basis for the disease 872 00:41:55,420 --> 00:41:58,555 are based around this amyloid beta process. 873 00:42:01,260 --> 00:42:04,190 So also really interesting, so somebody 874 00:42:04,190 --> 00:42:06,890 said, OK, so what if this is what's going on? 875 00:42:06,890 --> 00:42:09,544 What if we could manage to vaccinate people 876 00:42:09,544 --> 00:42:10,710 against Alzheimer's disease? 877 00:42:10,710 --> 00:42:16,430 What if we could manage to immunize them 878 00:42:16,430 --> 00:42:21,472 with something that removes these amyloid plaques? 879 00:42:21,472 --> 00:42:23,180 And I couldn't get the full copy of this, 880 00:42:23,180 --> 00:42:24,200 but I read the abstract. 881 00:42:24,200 --> 00:42:27,170 So these guys-- and this is a brand spanking new paper. 882 00:42:27,170 --> 00:42:31,310 This is in like the July 2008 issue of this journal. 883 00:42:31,310 --> 00:42:34,830 These guys were doing a clinical trial of this idea. 884 00:42:34,830 --> 00:42:37,400 So state 1 clinical trial, you do it 885 00:42:37,400 --> 00:42:39,020 on a small group of patients. 886 00:42:39,020 --> 00:42:41,390 I think they had 80 patients. 887 00:42:41,390 --> 00:42:45,107 And you kind of want to do it on patients who have nothing 888 00:42:45,107 --> 00:42:46,940 to lose, patients who have been unresponsive 889 00:42:46,940 --> 00:42:50,180 to other medications, patients who have a terminal 890 00:42:50,180 --> 00:42:51,060 disease of some sort. 891 00:42:51,060 --> 00:42:52,970 State 1 of clinical trials is the first time 892 00:42:52,970 --> 00:42:54,560 you try this drug on human beings. 893 00:42:54,560 --> 00:42:56,143 You've tried it on your animal models. 894 00:42:56,143 --> 00:43:01,070 It hasn't caused your rats to go into spasms or die or anything. 895 00:43:01,070 --> 00:43:03,230 We think it's safe, we think it's beneficial, 896 00:43:03,230 --> 00:43:05,070 let's move it to humans. 897 00:43:05,070 --> 00:43:08,480 And so what this immunization does 898 00:43:08,480 --> 00:43:17,000 is they have developed a protein that will kind of bond 899 00:43:17,000 --> 00:43:19,340 to the beta-amyloid fragments that 900 00:43:19,340 --> 00:43:24,480 make up these senile plaques and will remove them 901 00:43:24,480 --> 00:43:25,370 from the system. 902 00:43:25,370 --> 00:43:29,472 So it will actually go through and clean up 903 00:43:29,472 --> 00:43:30,680 all of these amyloid plaques. 904 00:43:30,680 --> 00:43:32,540 It will remove plaques. 905 00:43:32,540 --> 00:43:34,610 And so if the plaques themselves are 906 00:43:34,610 --> 00:43:39,200 what's causing Alzheimer's disease, then removing them 907 00:43:39,200 --> 00:43:41,950 should be beneficial. 908 00:43:41,950 --> 00:43:45,740 And so what they found is that the plaques were 909 00:43:45,740 --> 00:43:48,710 between OK and great, is that the immunization 910 00:43:48,710 --> 00:43:50,720 was between OK and great and for patients 911 00:43:50,720 --> 00:43:53,790 at removing these plaque. 912 00:43:53,790 --> 00:43:56,300 So compared to a control group who 913 00:43:56,300 --> 00:44:00,800 did not get the immunization, the patients who did, 914 00:44:00,800 --> 00:44:04,169 the experimental group, it removed somewhere-- 915 00:44:04,169 --> 00:44:06,710 for some patients, it was like less than half of the plaques. 916 00:44:06,710 --> 00:44:09,390 For some patients it was almost all of them. 917 00:44:09,390 --> 00:44:11,360 So there was definitely it's having some effect 918 00:44:11,360 --> 00:44:14,330 in decreasing the number of these beta-amyloid plaques 919 00:44:14,330 --> 00:44:16,790 in these patients' brains. 920 00:44:16,790 --> 00:44:21,350 But it did not improve either survival rates, either length 921 00:44:21,350 --> 00:44:25,510 of time from diagnosis to death for either group of patients. 922 00:44:25,510 --> 00:44:26,510 There was no difference. 923 00:44:26,510 --> 00:44:29,600 And it didn't change the rate at which the dementia progressed, 924 00:44:29,600 --> 00:44:31,400 the rate at which it got worse. 925 00:44:31,400 --> 00:44:36,590 So what this is implying is that is that whatever is going on 926 00:44:36,590 --> 00:44:38,852 with the amyloid protein process, 927 00:44:38,852 --> 00:44:41,060 and it still seems to be the best candidate for where 928 00:44:41,060 --> 00:44:43,460 the cause of this is, it's not simply 929 00:44:43,460 --> 00:44:45,740 the presence of the plaques in patients' brains 930 00:44:45,740 --> 00:44:47,450 that's causing this decline. 931 00:44:47,450 --> 00:44:50,210 The plaques also seem to be a secondary symptom rather than 932 00:44:50,210 --> 00:44:54,149 an immediate cause of Alzheimer's. 933 00:44:59,640 --> 00:45:02,023 All right, questions?