EXAMINING THE IMPACT OF SEX AND HORMONES ON THE PROGRESSION OF AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE - SUM…

Assistance award details

Assistance award identifier

ASST_NON_R00AG073452_075

FAIN

R00AG073452

Recipient

WASHINGTON UNIVERSITY, THE

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$479,201

Period

Sep 15, 2022 – Aug 31, 2028

Fiscal year

2025

Place of performance state

MO

Source file

FY2025_All_Assistance_Full_20261006.zip

Description

EXAMINING THE IMPACT OF SEX AND HORMONES ON THE PROGRESSION OF AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE - SUMMARY FEMALES MAY BE MORE SUSCEPTIBLE TO ALZHEIMER’S DISEASE (AD)-PATHOLOGY, YET, IN THE EARLY STAGES OF AD, FEMALES PERFORM BETTER ON VERBAL MEMORY TESTS THAN MALES WITH SIMILAR LEVELS OF PATHOLOGY. NONETHELESS, DESPITE THIS EARLY VERBAL MEMORY ADVANTAGE, AS DISEASE PROGRESSES, FEMALES SHOW FASTER COGNITIVE DECLINE. THUS, MORE RESEARCH IS NEEDED TO BETTER CHARACTERIZE SEX DIFFERENCES IN AD BIOMARKER PROGRESSION, AND TO CLARIFY POTENTIAL MECHANISMS OF COGNITIVE RESILIENCY OR VULNERABILITY TO AD-PATHOLOGY ACROSS THE DISEASE SPECTRUM. TO ADDRESS THESE CRITICAL KNOWLEDGE GAPS, I WILL CAPITALIZE ON OUR ONGOING LONGITUDINAL BIOMARKER STUDY WITH THE LARGEST AUTOSOMAL DOMINANT AD KINDRED DUE TO A SINGLE MUTATION (E280A) IN THE PRESENILIN-1 GENE (PSEN1). PSEN1 MUTATION CARRIERS ARE GENETICALLY DETERMINED TO DEVELOP EARLY-ONSET DEMENTIA, WITH MILD COGNITIVE IMPAIRMENT EMERGING AT A MEDIAN AGE OF 44 AND DEMENTIA AT AGE 49. THIS EXTRAORDINARY COHORT OFFERS THE OPPORTUNITY TO EXAMINE SEX DIFFERENCES IN AD WITH FEW AGE-RELATED CONFOUNDS AND METHODOLOGICAL CHALLENGES. TO THIS END, THE CANDIDATE PROPOSES: (1) TRAINING OBJECTIVES TO ESTABLISH EXPERTISE IN SEX BIOLOGY, LONGITUDINAL AND MULTIVARIATE MODELING, AND MULTIMODAL NEUROIMAGING DATA, WHICH TOGETHER WILL FURTHER CAREER DEVELOPMENT INTO AN INDEPENDENT CLINICAL RESEARCHER IN AD; (2) A RESEARCH OBJECTIVE TO EXAMINE SEX DIFFERENCES IN THE ACCUMULATION OF AD-RELATED PATHOLOGY, NEURODEGENERATION, AND COGNITIVE DECLINE, AND THE POTENTIAL ROLE OF STEROID HORMONES IN AUTOSOMAL DOMINANT AD; (3) A TEAM OF MENTORS AND ADVISORS TO ENSURE THE CANDIDATE’S SUCCESS, WITH EXPERTISE IN AUTOSOMAL DOMINANT AD (DR. YAKEEL QUIROZ), BIOLOGICAL SEX DIFFERENCES (DR. JILL GOLDSTEIN), SPORADIC AD (DR. REISA SPERLING), MULTIMODAL NEUROIMAGING (DR. CHEN), SEX-SPECIFIC DIFFERENCES AND RISK IN AD (DR. MICHELLE MIELKE), AND LONGITUDINAL AND MULTIVARI