Alzheimer's, Neuroimaging, Amyloid & Tau in the Frediericks Lab

Transcript

• 00:04Alzheimer's disease is a pathologic
• 00:07process where these proteins amyloid
• 00:08and tau accumulate in the
• 00:10brain.
• 00:11Both of these are naturally
• 00:13occurring proteins that exist in
• 00:14healthy forms in the body.
• 00:16They gunk up, they become
• 00:17abnormally folded, and and accumulate
• 00:19in ways that they wouldn't
• 00:20accumulate in health.
• 00:22And typically, it progresses
• 00:24along memory circuitry, and people
• 00:26start to experience difficulty with
• 00:28memory. But there are other
• 00:28forms of Alzheimer's that primarily
• 00:30involve other circuits that might
• 00:31have to do with language
• 00:32or with how we navigate
• 00:34space.
• 00:40Our lab is sort of
• 00:41interested in two axes around
• 00:43that typical patient that we
• 00:44picture, and one is the
• 00:45axis of preclinical disease or
• 00:46vulnerability. Before that patient develops
• 00:48those symptoms,
• 00:49she may have some pathology
• 00:51in her brain or often
• 00:52does.
• 00:52Pathology usually precedes
• 00:54evidence of clinical illness by
• 00:56ten or twenty years, and
• 00:57specific groups are more vulnerable
• 00:58to disease. So people with
• 01:00specific genotypes, women. We wanna
• 01:02understand those vulnerable states and
• 01:04some of the early changes
• 01:05that are happening in the
• 01:05brain during those times. We're
• 01:07also interested in heterogeneity.
• 01:09Not everyone with Alzheimer's has
• 01:10their biggest problems with memory.
• 01:11What happens when the disease
• 01:13infects other circuits and how
• 01:14can that give us more
• 01:15generalizable ideas about how the
• 01:17disease works?
• 01:23Tau has a number of
• 01:24effects that are being explored
• 01:25by scientists on a whole
• 01:26lot of different levels, and
• 01:27we typically look at that
• 01:29using neuroimaging.
• 01:31Functional MRI
• 01:32coupled with advanced PET scans
• 01:34like Tau PET, where we
• 01:34can actually see where the
• 01:35tau is in the brain.
• 01:37So one thing that we're
• 01:38very interested in right now
• 01:39is understanding these networks that
• 01:41are made up of hubs,
• 01:42spots in the brain that
• 01:43are connected to other spots
• 01:45in the brain, and we
• 01:46look at the properties of
• 01:47those circuits and how those
• 01:48might impact how quickly tau
• 01:50is traveling. It seems to
• 01:51travel along lines of functional
• 01:53circuitry. Typically when you have
• 01:54a clinical MRI, it's very
• 01:56structural. We're getting a really
• 01:57detailed look at the brain
• 01:58structures, at any changes in
• 02:00the white matter and the
• 02:01gray matter. We do that
• 02:02on a research basis too,
• 02:03but a lot of what
• 02:04we do is functional MRI.
• 02:06During those scans, a lot
• 02:07of the time we'll have
• 02:08patients doing something while they're
• 02:09in the scanner, watching movie
• 02:11clips or looking at postcard
• 02:12like images of scenes or
• 02:14faces. And the reason that
• 02:16we do that is that
• 02:17we think that by allowing
• 02:18people to be engaged in
• 02:20something like watching a movie,
• 02:21that can help draw out
• 02:22individual differences in the circuits
• 02:24that are involved in watching
• 02:26a movie and probably other
• 02:27circuits too.
• 02:32So we hope that this
• 02:33research will result in more
• 02:34generalizable models of how Alzheimer's
• 02:36pathology works across groups that
• 02:38have different levels of vulnerability.
• 02:40So it may be that
• 02:41different groups might benefit from
• 02:42different treatment targets or different
• 02:44treatment approaches, and that's something
• 02:45that we hope to shine
• 02:46a light on.
• 02:48Oftentimes, we have not identified
• 02:50people until they're very symptomatic
• 02:52and well on in illness
• 02:53and I think more and
• 02:54more we're able to identify
• 02:56people in these prodromal stages
• 02:57where we can't measure any
• 02:59memory decline on our cognitive
• 03:00tests but now we can
• 03:01visualize the proteins that are
• 03:03starting to accumulate. And the
• 03:04hope is that ultimately we
• 03:05could translate
• 03:07clinical trials back to those
• 03:08groups and stop the disease
• 03:10before it gets to the
• 03:11point of symptomatology.