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NIH grant 1K99AG095287-01A1: Investigating the Role of Sex, Sleep, and Menstrual Phase Interactions in Alzheimer's Disease Pathogenesis: A Remote Approach
Institute: {'code': 'AG', 'abbreviation': 'NIA', 'name': 'National Institute on Aging', 'admin_org_id': '12500002', 'admin_funding_url': ''}. PI: Negin Sattari Barabadi. Award: $127029.
Start: 2026-09-11T00:00:00.
Project Summary/Abstract
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that disproportionately affects women,
yet the biological mechanisms contributing to this sex disparity remain unclear. Sleep disturbances are a
modifiable risk factor for AD and may differentially affect women, particularly during midlife hormonal
transitions. This K99/R00 project investigates sex- and hormone-sensitive sleep neurophysiology—specifically
slow wave–sleep spindle (SW–SP) coupling—and its relationship to plasma AD biomarkers and sleep-
dependent memory consolidation (SDMC). The primary biomarker is phosphorylated tau (p-tau217), with
secondary markers including neurofilament light chain (NFL; neurodegeneration), glial fibrillary acidic protein
(GFAP; astrocytic activation), and amyloid-beta (Aβ42/40 ratio; plaque pathology).
In the K99 phase, 120 cognitively unimpaired older adults (ages 60–80) will complete a 6-night at-home
protocol including 3 nights of electroencephalogram (EEG) sleep recording and one at-home plasma collection.
This phase tests whether the interaction between sex and SW–SP coupling predicts p-tau217 and other
plasma biomarkers. We hypothesize that women will show reduced SW–SP coupling, which will be associated
with elevated p-tau217 levels.
The R00 phase extends this work to 118 midlife adults (ages 42–55; 59 regularly cycling women and 59 men),
investigating how menstrual cycle–related hormonal fluctuations modulate SW–SP coupling and its relationship
with plasma biomarkers and SDMC. Women will be tested during high (i.e., mid-luteal) and low (i.e., menses)
hormonal phases. Men, whose sex hormone levels remain relatively stable across time, will serve as an age-
matched comparison group to isolate the effects of cyclical hormonal variation in women from general sex
differences. We expect stronger SW–SP coupling, lower p-tau217, and better memory during high hormonal
phases in women.
This project leverages remote, ecologically valid methods to improve accessibility and inclusion of diverse
populations and applies both theory-driven and exploratory causal modeling to uncover mechanisms linking
sex, sleep, and AD risk. The candidate’s training plan integrates mentorship in ADRD, computational modeling,
sleep biomarkers, and hormone research to support a successful transition to independence and the
development of a precision-focused AD research program.document fetched 2026-09-20 02:42