Women accumulate Alzheimer's-related protein [Tau] faster

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BrianR
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Women accumulate Alzheimer's-related protein [Tau] faster

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ScienceDaily summary: https://www.sciencedaily.com/releases/2 ... 115423.htm
The first protein to aggregate in Alzheimer's is beta-amyloid. Men and women are equally affected by the first disease stages, and the analysis did not show any differences in the accumulation of beta-amyloid. Memory dysfunction arises later, when tau starts to accumulate. More women than men are affected by memory problems due to Alzheimer's, and it was for tau that the researchers found a higher rate of accumulation in women.

"Tau accumulation rates vary greatly between individuals of the same sex, but in the temporal lobe, which is affected in Alzheimer's disease, we found a 75% higher accumulation rate in women as a group compared to men," explains Ruben Smith, first author of the study.
Based on the open access paper:
https://academic.oup.com/brain/article/ ... 05/6015896
The accumulation rate of tau aggregates is higher in females and younger amyloid-positive subjects
Ruben Smith, et al
Brain, Volume 143, Issue 12, December 2020, Pages 3805–3815,
DOI: 10.1093/brain/awaa327
Interestingly, we found no independent effect of APOE ε4 positivity on the rate of tau accumulation.
(There were only 419 total participants, so, perhaps, just a lack of statistical power.)

It will be interesting to determine what the mechanism might be for the gendered differences in Tau accumulation (assuming results hold up in additional studies).
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floramaria
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Re: Women accumulate Alzheimer's-related protein [Tau] faster

Post by floramaria »

BrianR wrote:ScienceDaily summary: https://www.sciencedaily.com/releases/2 ... 115423.htm
The first protein to aggregate in Alzheimer's is beta-amyloid. Men and women are equally affected by the first disease stages, and the analysis did not show any differences in the accumulation of beta-amyloid. Memory dysfunction arises later, when tau starts to accumulate. More women than men are affected by memory problems due to Alzheimer's, and it was for tau that the researchers found a higher rate of accumulation in women.

"Tau accumulation rates vary greatly between individuals of the same sex, but in the temporal lobe, which is affected in Alzheimer's disease, we found a 75% higher accumulation rate in women as a group compared to men," explains Ruben Smith, first author of the study.
Based on the open access paper:
https://academic.oup.com/brain/article/ ... 05/6015896
The accumulation rate of tau aggregates is higher in females and younger amyloid-positive subjects
Ruben Smith, et al
Brain, Volume 143, Issue 12, December 2020, Pages 3805–3815,
DOI: 10.1093/brain/awaa327
Interestingly, we found no independent effect of APOE ε4 positivity on the rate of tau accumulation.
(There were only 419 total participants, so, perhaps, just a lack of statistical power.)

It will be interesting to determine what the mechanism might be for the gendered differences in Tau accumulation (assuming results hold up in additional studies).
Hi BrianR, wondering if this result could be related to testosterone levels in women.
NF52 recently posted this in another thread concerning testosterone.:

You may both be interested in this 2020 article looking at a possible association between ApoE4 women with low testosterone and risk of p-tau (phosphorylated tau). P-tau seems to be crucial ingredient in the development of Alzheimer's.

Here's the takeaway from a small study, and their recommendation for further research:
As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers....Our findings inform a knowledge gap in our understanding of greater Tauopathy in women versus men on the AD trajectory and in the repeated demonstration of a stronger APOE4 effect in women. Our findings may also help to enlighten disparities in the literature regarding an APOE4 and Tau relationship. This study represents a call to researchers and clinicians that it is equally important to examine the effects of testosterone on AD-related outcomes in women as it is in men, if not more.
Sex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone
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Re: Women accumulate Alzheimer's-related protein [Tau] faster

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BrianR wrote: ScienceDaily summary: https://www.sciencedaily.com/releases/2 ... 115423.htm
..."Tau accumulation rates vary greatly between individuals of the same sex, but in the temporal lobe, which is affected in Alzheimer's disease, we found a 75% higher accumulation rate in women as a group compared to men," explains Ruben Smith, first author of the study.
floramaria wrote:Hi BrianR, wondering if this result could be related to testosterone levels in women.NF52 recently posted this in another thread concerning testosterone...
As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers....Our findings inform a knowledge gap in our understanding of greater Tauopathy in women versus men on the AD trajectory and in the repeated demonstration of a stronger APOE4 effect in women. Our findings may also help to enlighten disparities in the literature regarding an APOE4 and Tau relationship. This study represents a call to researchers and clinicians that it is equally important to examine the effects of testosterone on AD-related outcomes in women as it is in men, if not more.
Thanks for linking these two studies, Floramaria! Here's a direct link to the article I quoted from: Sex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone
And here is the link to the topic it was posted on: Re: Question about testosterone
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BrianR
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Re: Women accumulate Alzheimer's-related protein [Tau] faster

Post by BrianR »

floramaria wrote:...Hi BrianR, wondering if this result could be related to testosterone levels in women.
NF52 recently posted this in another thread concerning testosterone.:...
Interesting, and plausible, thanks!
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Re: Women accumulate Alzheimer's-related protein [Tau] faster

Post by rsinda »

This is a fascinating topic! Now we may have yet another crucially important reason to look for and cautiously but adequately treat testosterone deficits in women, especially if they have Apo E4.
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Re: Women accumulate Alzheimer's-related protein [Tau] faster

Post by lucytownsend »

rsinda wrote:This is a fascinating topic! Now we may have yet another crucially important reason to look for and cautiously but adequately treat testosterone deficits in women, especially if they have Apo E4.
Hi rsinda,
Agreed fascinating topic. Are you familiar with the work of Dr. Ann Hathaway? https://annhathawaymd.com

Warmly,

Lucy
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