WEBVTT NOTE duration: "00:03:18.912" NOTE Confidence: 0.98490727 00:00:04.319 --> 00:00:06.500 Alzheimer's disease is a pathologic NOTE Confidence: 0.98490727 00:00:06.640 --> 00:00:08.400 process where these proteins amyloid NOTE Confidence: 0.98490727 00:00:08.400 --> 00:00:09.679 and tau accumulate in the NOTE Confidence: 0.98490727 00:00:09.679 --> 00:00:10.179 brain. NOTE Confidence: 0.99274826 00:00:11.119 --> 00:00:12.559 Both of these are naturally NOTE Confidence: 0.99274826 00:00:12.559 --> 00:00:14.000 occurring proteins that exist in NOTE Confidence: 0.99274826 00:00:14.000 --> 00:00:15.620 healthy forms in the body. NOTE Confidence: 0.966513 00:00:15.995 --> 00:00:17.275 They gunk up, they become NOTE Confidence: 0.966513 00:00:17.275 --> 00:00:19.275 abnormally folded, and and accumulate NOTE Confidence: 0.966513 00:00:19.275 --> 00:00:20.235 in ways that they wouldn't NOTE Confidence: 0.966513 00:00:20.235 --> 00:00:21.295 accumulate in health. NOTE Confidence: 0.9220012 00:00:21.675 --> 00:00:23.055 And typically, it progresses NOTE Confidence: 0.98149925 00:00:23.515 --> 00:00:25.775 along memory circuitry, and people NOTE Confidence: 0.98149925 00:00:25.915 --> 00:00:27.515 start to experience difficulty with NOTE Confidence: 0.98149925 00:00:27.515 --> 00:00:28.410 memory. But there are other NOTE Confidence: 0.98149925 00:00:28.410 --> 00:00:30.090 forms of Alzheimer's that primarily NOTE Confidence: 0.98149925 00:00:30.090 --> 00:00:31.370 involve other circuits that might NOTE Confidence: 0.98149925 00:00:31.370 --> 00:00:32.490 have to do with language NOTE Confidence: 0.98149925 00:00:32.490 --> 00:00:33.610 or with how we navigate NOTE Confidence: 0.98149925 00:00:33.610 --> 00:00:34.110 space. NOTE Confidence: 0.9704098 00:00:40.025 --> 00:00:40.985 Our lab is sort of NOTE Confidence: 0.9704098 00:00:40.985 --> 00:00:42.665 interested in two axes around NOTE Confidence: 0.9704098 00:00:42.665 --> 00:00:43.784 that typical patient that we NOTE Confidence: 0.9704098 00:00:43.784 --> 00:00:44.745 picture, and one is the NOTE Confidence: 0.9704098 00:00:44.745 --> 00:00:46.265 axis of preclinical disease or NOTE Confidence: 0.9704098 00:00:46.265 --> 00:00:48.265 vulnerability. Before that patient develops NOTE Confidence: 0.9704098 00:00:48.265 --> 00:00:49.004 those symptoms, NOTE Confidence: 0.9727202 00:00:49.385 --> 00:00:50.585 she may have some pathology NOTE Confidence: 0.9727202 00:00:50.585 --> 00:00:51.545 in her brain or often NOTE Confidence: 0.9727202 00:00:51.545 --> 00:00:51.960 does. NOTE Confidence: 0.9930432 00:00:52.360 --> 00:00:53.739 Pathology usually precedes NOTE Confidence: 0.98026913 00:00:54.120 --> 00:00:55.559 evidence of clinical illness by NOTE Confidence: 0.98026913 00:00:55.559 --> 00:00:56.760 ten or twenty years, and NOTE Confidence: 0.98026913 00:00:56.760 --> 00:00:58.199 specific groups are more vulnerable NOTE Confidence: 0.98026913 00:00:58.199 --> 00:00:59.559 to disease. So people with NOTE Confidence: 0.98026913 00:00:59.559 --> 00:01:01.720 specific genotypes, women. We wanna NOTE Confidence: 0.98026913 00:01:01.720 --> 00:01:03.640 understand those vulnerable states and NOTE Confidence: 0.98026913 00:01:03.640 --> 00:01:04.600 some of the early changes NOTE Confidence: 0.98026913 00:01:04.600 --> 00:01:05.400 that are happening in the NOTE Confidence: 0.98026913 00:01:05.400 --> 00:01:06.955 brain during those times. We're NOTE Confidence: 0.98026913 00:01:06.955 --> 00:01:08.255 also interested in heterogeneity. NOTE Confidence: 0.98621655 00:01:08.555 --> 00:01:09.995 Not everyone with Alzheimer's has NOTE Confidence: 0.98621655 00:01:09.995 --> 00:01:11.275 their biggest problems with memory. NOTE Confidence: 0.98621655 00:01:11.275 --> 00:01:12.635 What happens when the disease NOTE Confidence: 0.98621655 00:01:12.635 --> 00:01:14.235 infects other circuits and how NOTE Confidence: 0.98621655 00:01:14.235 --> 00:01:15.275 can that give us more NOTE Confidence: 0.98621655 00:01:15.275 --> 00:01:16.875 generalizable ideas about how the NOTE Confidence: 0.98621655 00:01:16.875 --> 00:01:17.694 disease works? NOTE Confidence: 0.9661472 00:01:22.610 --> 00:01:23.569 Tau has a number of NOTE Confidence: 0.9661472 00:01:23.569 --> 00:01:25.090 effects that are being explored NOTE Confidence: 0.9661472 00:01:25.090 --> 00:01:26.290 by scientists on a whole NOTE Confidence: 0.9661472 00:01:26.290 --> 00:01:27.490 lot of different levels, and NOTE Confidence: 0.9661472 00:01:27.490 --> 00:01:28.770 we typically look at that NOTE Confidence: 0.9661472 00:01:28.770 --> 00:01:29.590 using neuroimaging. NOTE Confidence: 0.97574794 00:01:30.530 --> 00:01:31.509 Functional MRI NOTE Confidence: 0.9399291 00:01:31.890 --> 00:01:33.569 coupled with advanced PET scans NOTE Confidence: 0.9399291 00:01:33.569 --> 00:01:34.450 like Tau PET, where we NOTE Confidence: 0.9399291 00:01:34.450 --> 00:01:35.409 can actually see where the NOTE Confidence: 0.9399291 00:01:35.409 --> 00:01:36.630 tau is in the brain. NOTE Confidence: 0.98577285 00:01:37.384 --> 00:01:38.185 So one thing that we're NOTE Confidence: 0.98577285 00:01:38.185 --> 00:01:39.305 very interested in right now NOTE Confidence: 0.98577285 00:01:39.305 --> 00:01:41.064 is understanding these networks that NOTE Confidence: 0.98577285 00:01:41.064 --> 00:01:42.424 are made up of hubs, NOTE Confidence: 0.98577285 00:01:42.424 --> 00:01:43.305 spots in the brain that NOTE Confidence: 0.98577285 00:01:43.305 --> 00:01:44.664 are connected to other spots NOTE Confidence: 0.98577285 00:01:44.664 --> 00:01:45.625 in the brain, and we NOTE Confidence: 0.98577285 00:01:45.625 --> 00:01:46.825 look at the properties of NOTE Confidence: 0.98577285 00:01:46.825 --> 00:01:48.185 those circuits and how those NOTE Confidence: 0.98577285 00:01:48.185 --> 00:01:49.625 might impact how quickly tau NOTE Confidence: 0.98577285 00:01:49.625 --> 00:01:50.905 is traveling. It seems to NOTE Confidence: 0.98577285 00:01:50.905 --> 00:01:52.445 travel along lines of functional NOTE Confidence: 0.96437746 00:01:52.960 --> 00:01:54.399 circuitry. Typically when you have NOTE Confidence: 0.96437746 00:01:54.399 --> 00:01:55.680 a clinical MRI, it's very NOTE Confidence: 0.96437746 00:01:55.680 --> 00:01:57.040 structural. We're getting a really NOTE Confidence: 0.96437746 00:01:57.040 --> 00:01:58.479 detailed look at the brain NOTE Confidence: 0.96437746 00:01:58.479 --> 00:02:00.000 structures, at any changes in NOTE Confidence: 0.96437746 00:02:00.000 --> 00:02:00.799 the white matter and the NOTE Confidence: 0.96437746 00:02:00.799 --> 00:02:02.079 gray matter. We do that NOTE Confidence: 0.96437746 00:02:02.079 --> 00:02:03.280 on a research basis too, NOTE Confidence: 0.96437746 00:02:03.280 --> 00:02:03.920 but a lot of what NOTE Confidence: 0.96437746 00:02:03.920 --> 00:02:05.355 we do is functional MRI. NOTE Confidence: 0.9740901 00:02:05.835 --> 00:02:07.035 During those scans, a lot NOTE Confidence: 0.9740901 00:02:07.035 --> 00:02:07.755 of the time we'll have NOTE Confidence: 0.9740901 00:02:07.755 --> 00:02:09.035 patients doing something while they're NOTE Confidence: 0.9740901 00:02:09.035 --> 00:02:10.635 in the scanner, watching movie NOTE Confidence: 0.9740901 00:02:10.635 --> 00:02:12.475 clips or looking at postcard NOTE Confidence: 0.9740901 00:02:12.475 --> 00:02:14.155 like images of scenes or NOTE Confidence: 0.9740901 00:02:14.155 --> 00:02:15.675 faces. And the reason that NOTE Confidence: 0.9740901 00:02:15.675 --> 00:02:16.555 we do that is that NOTE Confidence: 0.9740901 00:02:16.555 --> 00:02:17.915 we think that by allowing NOTE Confidence: 0.9740901 00:02:17.915 --> 00:02:19.514 people to be engaged in NOTE Confidence: 0.9740901 00:02:19.514 --> 00:02:20.880 something like watching a movie, NOTE Confidence: 0.9740901 00:02:21.040 --> 00:02:22.080 that can help draw out NOTE Confidence: 0.9740901 00:02:22.080 --> 00:02:24.160 individual differences in the circuits NOTE Confidence: 0.9740901 00:02:24.160 --> 00:02:25.600 that are involved in watching NOTE Confidence: 0.9740901 00:02:25.600 --> 00:02:26.880 a movie and probably other NOTE Confidence: 0.9740901 00:02:26.880 --> 00:02:27.700 circuits too. NOTE Confidence: 0.99484 00:02:32.080 --> 00:02:33.040 So we hope that this NOTE Confidence: 0.99484 00:02:33.040 --> 00:02:34.320 research will result in more NOTE Confidence: 0.99484 00:02:34.320 --> 00:02:36.405 generalizable models of how Alzheimer's NOTE Confidence: 0.99484 00:02:36.405 --> 00:02:38.005 pathology works across groups that NOTE Confidence: 0.99484 00:02:38.005 --> 00:02:39.385 have different levels of vulnerability. NOTE Confidence: 0.9849707 00:02:39.925 --> 00:02:40.805 So it may be that NOTE Confidence: 0.9849707 00:02:40.805 --> 00:02:42.165 different groups might benefit from NOTE Confidence: 0.9849707 00:02:42.165 --> 00:02:43.605 different treatment targets or different NOTE Confidence: 0.9849707 00:02:43.605 --> 00:02:45.285 treatment approaches, and that's something NOTE Confidence: 0.9849707 00:02:45.285 --> 00:02:45.965 that we hope to shine NOTE Confidence: 0.9849707 00:02:45.965 --> 00:02:46.825 a light on. NOTE Confidence: 0.9571882 00:02:48.005 --> 00:02:49.865 Oftentimes, we have not identified NOTE Confidence: 0.9571882 00:02:49.925 --> 00:02:51.720 people until they're very symptomatic NOTE Confidence: 0.9571882 00:02:51.780 --> 00:02:52.980 and well on in illness NOTE Confidence: 0.9571882 00:02:52.980 --> 00:02:53.940 and I think more and NOTE Confidence: 0.9571882 00:02:53.940 --> 00:02:55.620 more we're able to identify NOTE Confidence: 0.9571882 00:02:55.620 --> 00:02:57.320 people in these prodromal stages NOTE Confidence: 0.9571882 00:02:57.380 --> 00:02:59.060 where we can't measure any NOTE Confidence: 0.9571882 00:02:59.060 --> 00:03:00.419 memory decline on our cognitive NOTE Confidence: 0.9571882 00:03:00.419 --> 00:03:01.380 tests but now we can NOTE Confidence: 0.9571882 00:03:01.380 --> 00:03:02.820 visualize the proteins that are NOTE Confidence: 0.9571882 00:03:02.820 --> 00:03:04.260 starting to accumulate. And the NOTE Confidence: 0.9571882 00:03:04.260 --> 00:03:05.380 hope is that ultimately we NOTE Confidence: 0.9571882 00:03:05.380 --> 00:03:06.040 could translate NOTE Confidence: 0.99564797 00:03:06.555 --> 00:03:07.995 clinical trials back to those NOTE Confidence: 0.99564797 00:03:07.995 --> 00:03:09.514 groups and stop the disease NOTE Confidence: 0.99564797 00:03:09.514 --> 00:03:10.635 before it gets to the NOTE Confidence: 0.99564797 00:03:10.635 --> 00:03:11.775 point of symptomatology.