EXPLORING COMMON BIOLOGICAL PATHWAYS UNDERLYING INSULIN RESISTANCE AND ALZHEIMER DISEASE USING GENETIC AND…

Assistance award details

Assistance award identifier

ASST_NON_R00AG066849_075

FAIN

R00AG066849

Recipient

UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$794,831

Period

Apr 1, 2021 – Jul 31, 2025

Fiscal year

2022

Place of performance state

TX

Source file

FY2022_All_Assistance_Full_20261006.zip

Description

EXPLORING COMMON BIOLOGICAL PATHWAYS UNDERLYING INSULIN RESISTANCE AND ALZHEIMER DISEASE USING GENETIC AND OMIC TOOLS - PROJECT SUMMARY / ABSTRACT INSULIN RESISTANCE (IR) IS A MAJOR RISK FACTOR FOR ALZHEIMER’S DISEASE (AD) BUT THE MECHANISMS BY WHICH IR PREDISPOSES TO AD IS UNKNOWN, NOTABLY, IF IR IS CAUSALLY RELATED TO AD AND WHICH REGULATORY MECHANISMS UNDERLIE IR AND CONTRIBUTE TO AD. THE PROPOSAL IS DESIGNED TO ADDRESS THESE CRITICAL GAPS IN SCIENTIFIC KNOWLEDGE BY USING OMICS TO EVALUATE THE CAUSAL RELATIONSHIP OF IR ON AD AND TO REVEAL NEW REGULATORY MECHANISMS INVOLVED IN IR AND AD. THE PRINCIPAL INVESTIGATOR (PI), DR. SARNOWSKI, IS A STATISTICAL GENETICIST AND AN EARLY CAREER INVESTIGATOR WITH A RESEARCH FOCUS ON THE IDENTIFICATION OF GENETIC AND ENVIRONMENTAL RISK FACTORS OF COMPLEX TRAITS. THE LONG-TERM GOAL OF THIS PROJECT IS TO IDENTIFY INDIVIDUALS WHO WILL BENEFIT FROM TREATMENTS IMPROVING INSULIN SENSITIVITY TO BETTER PREVENT, DELAY OR STOP THE PROGRESSION OF AD. THE OVERALL OBJECTIVE IS TO BETTER CHARACTERIZE MECHANISMS BY WHICH IR CONTRIBUTES TO AD AND EVALUATE HOW THEY MAY DIFFER FROM KNOWN MECHANISMS INVOLVED IN AD PATHOGENESIS. THE CENTRAL HYPOTHESIS IS THAT OMICS WILL HELP TO BETTER UNDERSTAND AND CHARACTERIZE THE RELATIONSHIPS BETWEEN IR AND AD. THE RATIONALE IS THAT OMICS WILL HELP TO DISENTANGLE THE MODE OF ACTION OF IR ON AD AND IDENTIFY TARGETS FOR PREVENTIVE AND THERAPEUTIC INTERVENTIONS. GUIDED BY STRONG PRELIMINARY RESULTS IN THE FRAMINGHAM HEART STUDY, THE HYPOTHESIS WILL BE TESTED THROUGH THREE SPECIFIC AIMS: 1) DETERMINE IF IR IS CAUSALLY RELATED TO AD IN A MENDELIAN RANDOMIZATION (MR) FRAMEWORK WITH VARIOUS GENETIC INSTRUMENT VARIABLES (IVS); 2) CHARACTERIZE MOLECULAR SIGNATURES OF IR ASSOCIATED WITH AD USING BRAIN AND BLOOD OMIC DATA; AND 3) DEVELOP A JOINT TEST TO EVALUATE THE GENETIC CONTRIBUTION AT IR SIGNATURES ASSOCIATED WITH AD. IN AIM 1, GENETIC IVS, INCLUDING STANDARD AND PATHWAY-SPECIFIC GENETIC RISK SCORES AND PREDICTORS