Blood Biomarkers May Help Early Detection of Alzheimer's

Bloomberg

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00:00When it comes to neurological problems, what are the difference in what affects women versus men?

00:06It's a pleasure to join you. The short answer to that is that we know the statistics of what

00:14are the diseases that afflict women at a higher prevalence than men, and one of them is Alzheimer's

00:22disease. But it would not be correct to say that we understand the why. And I think this is exactly

00:29why we need to be doing research, because getting the answer to why are women's brains more vulnerable

00:38to Alzheimer's disease and other kinds of neurodegenerative disorders may hold the key

00:43to understanding how these diseases strike the vulnerable brain. And so that knowledge will

00:49definitely help women. But I think beyond that would help us understand what are the key factors

00:55that make the aging brains vulnerable to Alzheimer's disease.

00:59At this point, do we know, what do we know? What are the clues or what are the hypotheses that

01:05medical professionals have established?

01:10A central hypothesis that we and others are following is that in women's lives, there is a huge

01:20physiological transition in midlife due to menopause. That shift in hormones that the brain and other

01:30organs see is unique to women. It happens in men, but at a much later stage in their life. And so what we

01:38are doing at Mount Sinai is to specifically query the impact that lower levels of estrogen may have

01:49on the cells that form the vasculature of the brain, the protective barriers of the brain and other

01:57cells within the brain.

01:58So is a fix, an easy fix, just keeping the hormone levels higher? And I know that there are consequences

02:03to doing that potentially. Like, how do we think about it? Or how do you guys think about R&D and what can

02:08be done to help women since they are certainly, it sounds like, more vulnerable as a result when it comes to

02:14Alzheimer's? Absolutely. We certainly hope that for those who can get hormone replacement therapy,

02:23that may diminish their risk to a certain extent. But the question is, when do those hormones need to

02:31be started? And we think it needs to be perimenopause. You cannot wait too long before starting them.

02:37The second question is, how long do you keep those hormones? As you alluded to it,

02:46those hormones also increase the risk of other things such as cancers. And those risks increase

02:53as women age. So how long do you keep someone on hormones in order to decrease their risk for

02:59Alzheimer's disease, which is a late life phenomenon? And then the third question is, for the many women

03:04who actually cannot be on those hormones, what can we discover about what those hormones do and just

03:12go ahead and develop drugs and interventions that activate or deactivate those pathways?

03:18What about genetic components? If somebody else in the family has had Alzheimer's, that trait being

03:24passed down, does that happen? That's an excellent question. And in fact, one of the most prevalent

03:31genetic risk factors for Alzheimer's disease, the ApoE4 allele, we think interacts with hormones

03:40in exerting its effect on Alzheimer's disease. Now, the question of heritability of Alzheimer's

03:46goes beyond just ApoE4. And that in of itself is a really big area of research. There are other

03:54components of the disease, such as metabolism and mitochondria that we inherit from the maternal side,

04:04for instance, that could be contributing to this heritability. But even beyond that, there are aspects

04:11of our ancestry that continue within us in forms that we currently don't fully grasp. And I hope we

04:22will understand in the future to, again, contribute to better therapeutic developments.

04:26So talk to us a little bit about, you've done a lot of work when it comes to blood biomarkers. Why might this

04:31be important here?

04:35Blood biomarkers are very exciting because similar to other disorders, such as cardiovascular disease, cancer,

04:44kidney, liver disease, you really want to detect disease before individuals have prominent symptoms

04:52that bring them to the medical attention. And in the case of Alzheimer's and other kinds of neurodegenerative

04:57disorders, those are cognitive impairment and ultimately dementia. At the point that someone has very

05:03significant cognitive changes, we think we could potentially slow down disease progression. But to say

05:10that we can stall it or have game-changing treatments completely change someone's brain trajectory would be

05:18not realistic. So these blood biomarkers can detect risk of future symptoms with increasingly better

05:31predictive ability. One thing that I should mention is that we don't think that the pathologies that

05:38eventually lead to dementia start at the time that symptoms present. They really start decades before.

05:44Wow.

05:44And these blood biomarkers for Alzheimer's disease are detecting that. My lab works on expanding that

05:51panel because right now we are detecting only a few aspects of the disease. We think a key component

05:58of Alzheimer's and other neurodegenerative diseases are the changes that happen to the blood vessels of the

06:04brain. And at the moment, we have no biomarkers that detect vascular pathologies with great precision.

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