# Biological and lifestyle factors contributing to Tau in women at risk for Alzheimer's disease.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $1,025,931

## Abstract

PROJECT SUMMARY/ABSTRACT Growing evidence reports that women show a more aggressive profile of
Alzheimer's disease (AD) than men with greater pathological tau burden and steeper cognitive decline; yet the
reasons for these sex differences are poorly understood. Sex differences in AD point to sex-disparate causal
pathways as well as sex-specific therapeutic targets. Neuroinflammation (N-Inf) is one candidate casual pathway
that shows sex disparities and plays a central role in AD pathogenesis with close ties to both tau and cognitive
decline. Women tend to have a more robust immune/inflammatory response and comprise 80% of autoimmune
disease cases. Moreover, our own preliminary work in the Alzheimer's Disease Neuroimaging Initiative indicated
that women may be more susceptible than men to the adverse effect of N-Inf, particularly the markers of TNFα,
IL6 and their receptors on cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and cognitive function.
There are also lifestyle factors such as physical activity and obstructive sleep apnea (OSA) known to influence N-
Inf and relate to tau and cognitive decline and to do so differently in women versus men. Our own preliminary data
highlight sedentary behavior and obstructive sleep apnea as two modifiable risk factors that show strong
associations with N-Inf, tau and/or cognitive function in older women, and thus stress the need to further
understand how and to what degree these lifestyle interventions could reduce AD risk. Together, these findings
led us to this proposed observational study that will examine how N-Inf markers (specifically TNFα, TNFR2, IL6
and IL6R) and the modifiable risk factors that influence N-Inf relate to tau accumulation and cognitive decline in
older women at-risk for AD by way of mild cognitive deficits and genetic risk. Moreover, we will explore how sex
hormones, particularly testosterone, contribute to these relationships given their anti-inflammatory and central
nervous system effects and often contributing role to sex differences. To achieve this, we propose to measure
CSF N-Inf markers, physical activity, OSA, and circulating sex hormones in a sample of 100 older women at-risk
for AD and relate these measures to changes in cognitive function and accumulation of tau, measured via
positron emission tomography (PET), over a two-year period. This study will build upon a state-funded, pilot
study by increasing the sample size and adding longitudinal assessments in order to conduct a rigorous
examination of our hypotheses. In keeping with NIH research priorities, after 5 years of potential funding, this
project will help to close critical gaps in our understanding of sex differences in AD by examining under-explored
yet highly-relevant mechanisms that may contribute to the greater pathology and steeper cognitive decline in
women on the AD trajectory. Furthermore, our findings will inform risk reduction strategies that influence these
mechanisms – an important focus ...

## Key facts

- **NIH application ID:** 10591159
- **Project number:** 1R01AG080663-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** SARAH BANKS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,025,931
- **Award type:** 1
- **Project period:** 2023-09-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10591159

## Citation

> US National Institutes of Health, RePORTER application 10591159, Biological and lifestyle factors contributing to Tau in women at risk for Alzheimer's disease. (1R01AG080663-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10591159. Licensed CC0.

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