LIPID AND MATRISOME DYSREGULATION IN DOWN SYNDROME AND ALZHEIMER'S DISEASE GLIA - PROJECT SUMMARY IN ADDITI…

Assistance award details

Assistance award identifier

ASST_NON_K00AG086925_075

FAIN

K00AG086925

Recipient

TRUSTEES OF BOSTON UNIVERSITY

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.310

Total obligated

$93,574

Period

Jul 1, 2024 – Apr 30, 2030

Fiscal year

2026

Place of performance state

MA

Source file

FY2026_All_Assistance_Full_20261006.zip

Description

LIPID AND MATRISOME DYSREGULATION IN DOWN SYNDROME AND ALZHEIMER'S DISEASE GLIA - PROJECT SUMMARY IN ADDITION TO INTELLECTUAL DISABILITY, INDIVIDUALS WITH DOWN SYNDROME (DS, TRISOMY 21, TS21) HAVE AN INCREASED RISK FOR MANY OTHER HEALTH CONDITIONS, INCLUDING ALZHEIMER’S DISEASE (AD). DS IS THE LEADING GENETIC RISK FACTOR FOR AD, AND NEARLY 90% OF INDIVIDUALS WITH DS DEVELOP AD (DS-AD). BETA-AMYLOID (AΒ) PLAQUES AND TAU TANGLES, CHARACTERISTIC AD PATHOLOGY, BEGIN ACCUMULATING IN DS BRAINS EARLIER THAN IN THE GENERAL POPULATION, AND MOST INDIVIDUALS WITH DS ARE DIAGNOSED WITH DS-AD IN THEIR EARLY TO MID-50S. BASAL FOREBRAIN CHOLINERGIC NEURONS (BFCNS), INVOLVED IN AROUSAL, LEARNING, ATTENTION, AND MEMORY, ARE A SUSCEPTIBLE POPULATION PRONE TO DEGENERATION IN DS-AD AS WELL AS OTHER NEURODEGENERATIVE DISEASES, INCLUDING AD, PARKINSON’S DISEASE (PD), AND DEMENTIA WITH LEWY BODIES (DLB). LITTLE IS KNOWN ABOUT BFCN DEVELOPMENT AND MOLECULAR MECHANISMS UNDERLYING VULNERABILITY. LIMITED ANALYSIS OF HUMAN DS TISSUE SUGGESTS FEWER BFCNS POPULATE THE BASAL FOREBRAIN, HOWEVER, IT REMAINS UNCLEAR WHETHER THE REDUCTION IS DUE TO DEVELOPMENTAL DEFICITS, ACCELERATED DEGENERATION, OR A COMBINATION OF BOTH. THE GOALS OF THE F99 PRE-DOCTORAL PROPOSAL ARE TO 1) DETERMINE WHETHER FEWER BFCNS AND AD PATHOLOGY ARE PRESENT IN THE EARLY POSTNATAL DS BASAL FOREBRAIN, 2) IDENTIFY UNDERLYING MOLECULAR SIGNATURES THAT MAY CONTRIBUTE TO THE SUSCEPTIBILITY OF BFCNS LATER IN LIFE, AND 3) MODEL BFCN DEVELOPMENT IN VITRO USING ISOGENIC OF TS21 AND CONTROL INDUCED PLURIPOTENT STEM CELLS. THE GOALS OF THE K00 POST-DOCTORAL PROPOSAL ARE TO 1) ANALYZE TISSUE ACROSS THE LIFESPAN AT DIFFERENT DISEASE STAGES TO DETERMINE THE TEMPORAL ORDER OF AD PATHOLOGY ACCUMULATION IN THE DS BASAL FOREBRAIN, AND 2) SEQUENCE BASAL FOREBRAIN TISSUE FROM DS-AD, AD, PD, AND DLB TO DETERMINE IF SHARED MECHANISMS UNDERLIE BFCN VULNERABILITY ACROSS SEVERAL NEURODEGENERATIVE DISEASES. THIS F99 PROPOSAL WILL BE THE FIRST STU