MENOPAUSE, HORMONE THERAPY AND ALZHEIMER'S DISEASE CLINICOPATHOLOGY: AN IN VIVO PERSPECTIVE - PROJECT SUMMA…

Assistance award details

Assistance award identifier

ASST_NON_R00AG083063_075

FAIN

R00AG083063

Recipient

THE GENERAL HOSPITAL CORPORATION

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$249,000

Period

Jun 1, 2024 – May 31, 2029

Fiscal year

2026

Place of performance state

MA

Source file

FY2026_All_Assistance_Full_20261006.zip

Description

MENOPAUSE, HORMONE THERAPY AND ALZHEIMER'S DISEASE CLINICOPATHOLOGY: AN IN VIVO PERSPECTIVE - PROJECT SUMMARY / ABSTRACT IN THE UNITED STATES, APPROXIMATELY 6.2 MILLION PEOPLE LIVE WITH A CLINICAL DIAGNOSIS OF ALZHEIMER DISEASE (AD). POSTMENOPAUSAL WOMEN ACCOUNT FOR UP TO 70% OF THEM. THE OVERALL GOAL OF THIS PROPOSED RESEARCH IS TO ELUCIDATE THE PROGRESSIVE PATHOPHYSIOLOGICAL MECHANISMS BY WHICH MENOPAUSAL HORMONE THERAPY (HT) INFLUENCES THE RISK OF AD DEMENTIA IN WOMEN. THE APPLICANT’S PRIOR WORK SHOWED THAT THE TIMING OF HT USE RELATIVE TO MENOPAUSE ONSET INFLUENCES FEMALES’ SUSCEPTIBILITY TO THE DEPOSITION AD PATHOLOGY IN LATER LIFE. IT IS CRITICAL THAT LONGITUDINAL COHORT STUDIES AND RANDOMIZED CONTROLLED TRIALS ARE CONDUCTED TO SUBSTANTIATE THESE FINDINGS. DURING THE K99 PHASE, THE APPLICANT WILL COMBINE THREE OBSERVATIONAL STUDIES (N=772) WITH LONGITUDINAL BIOMARKERS OF AD, AS MEASURED WITH POSITRON EMISSION TOMOGRAPHY (PET), TO DETERMINE TO INFLUENCE OF HT AND ITS TIMING ON NEOCORTICAL AΒ ACCUMULATION (OVER 6.5 YEARS; AIM 1), REGION-SPECIFIC TAU ACCUMULATION (OVER 4.2 YEARS; AIM 1) AND COGNITIVE DECLINE (OVER 7.4 YEARS; AIM 2). TO ACHIEVE THESE AIMS, THE APPLICANT WILL LEVERAGE THEIR EXISTING STRENGTHS IN NEUROIMAGING, GENETIC-RISK, COGNITIVE NEUROSCIENCE AND BIG DATA AND GAIN EXPERTISE IN FOLLOWING FIVE AREAS OF TRAINING: (1) PET-NEUROIMAGING (2) BIOFLUIDS (3) STATISTICS (4) HORMONES AND (5) CLINICAL TRIALS (ANALYTICAL APPROACHES). WITH THESE SKILLS, THE APPLICANT WILL BE WELL POSITIONED IN THE R00 PHASE TO CONDUCT THE FINAL AIM: TO DETERMINE HOW EARLY AND LATE HT RANDOMIZATION IMPACTS THE PATHOLOGICAL PROGRESSION OF AD, RELATIVE TO RESPECTIVE PLACEBO GROUPS, AS MEASURED WITH MULTIPLE PLASMA AD BIOMARKERS (AB42/AB40, P-TAU181, P-TAU217, P-TAU231; AIM 3). IN THE R00, THE APPLICANT WILL UTILIZE EXISTING SAMPLES FROM THE WOMEN HEALTH INITIATIVE; A LANDMARK RANDOMIZED CONTROLLED TRIAL ON HT (N=3,472). FURTHER, NON-AD SPECIFIC PLASMA BIOMARKERS WILL BE INTE