ASSOCIATIONS OF MITOCHONDRIAL DNA ALTERATIONS WITH ALZHEIMER'S DISEASE RELATED BRAIN HEALTH - ABSTRACT DEME…

Assistance award details

Assistance award identifier

ASST_NON_R00AG083214_075

FAIN

R00AG083214

Recipient

UNIVERSITY OF ILLINOIS

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$493,018

Period

Aug 15, 2023 – Jul 31, 2028

Fiscal year

2025

Place of performance state

IL

Source file

FY2025_All_Assistance_Full_20261006.zip

Description

ASSOCIATIONS OF MITOCHONDRIAL DNA ALTERATIONS WITH ALZHEIMER'S DISEASE RELATED BRAIN HEALTH - ABSTRACT DEMENTIA IS A MAJOR GLOBAL HEALTH CHALLENGE THAT LACKS EFFECTIVE TREATMENT AND EARLY DIAGNOSIS TOOLS. ALZHEIMER’S DISEASE (AD) COMPRISES 70% OF ALL DEMENTIA SYNDROMES. THE LANCET COMMISSION RECENTLY URGED A LIFE-COURSE MODEL OF AD PREVENTION, PROVIDING IMPETUS FOR THE DEVELOPMENT OF SCALABLE EARLY BIOMARKERS. MITOCHONDRIA PLAY A CRITICAL BIOENERGETIC ROLE IN MAINTAINING PHYSIOLOGIC HOMEOSTASIS, PARTICULARLY FOR HIGH ENERGY DEMAND ORGANS, LIKE THE BRAIN. MITOCHONDRIAL DNA (MTDNA) COPY NUMBER (MTDNA-CN), A QUANTITATIVE INDICATOR OF MITOCHONDRIAL FUNCTION, IS STRONGLY ASSOCIATED WITH AD IN OLDER ADULTS. GROWING EVIDENCE ALSO IMPLICATES MTDNA MUTATION LOAD, OR MTDNA HETEROPLASMY (MTDNA-HET), IN AD. DESPITE THE ACCUMULATING EVIDENCE FOR A KEY ROLE OF THESE BLOOD INDICATORS IN COGNITIVE DECLINE AND AD IN OLDER ADULTS, THERE IS A PAUCITY OF RESEARCH EXAMINING THEIR RELATIONSHIPS IN MIDLIFE, A CRITICAL TIME WHEN PREVENTIVE INTERVENTIONS MAY BE MOST EFFECTIVE. MOREOVER, THE RELATIONSHIPS BETWEEN THESE MTDNA ALTERATIONS AND EARLY EMERGING AD-RELATED NEUROBIOLOGICAL SUBSTRATES IS UNCLEAR. WHILE CARDIOVASCULAR DISEASE (CVD) RISK FACTORS HAVE ALSO BEEN ASSOCIATED WITH MTDNA ALTERATIONS, THE TEMPORAL ASSOCIATIONS ARE NOT FULLY DISCERNED. WHETHER MTDNA ALTERATIONS COULD MEDIATE THE WELL-KNOWN BUT LESS WELL UNDERSTOOD ASSOCIATIONS OF HEART AND BRAIN HEALTH IS UNKNOWN. OUR CENTRAL HYPOTHESIS IS THAT MTDNA ALTERATIONS ARE ASSOCIATED WITH COGNITIVE DECLINE AND AD-RELATED NEUROBIOLOGICAL SUBSTRATES IN MIDLIFE AND MEDIATE THE ASSOCIATIONS OF EARLY LIFE CVD RISK FACTORS WITH MIDLIFE BRAIN HEALTH. TO TEST THIS HYPOTHESIS, WE WILL LEVERAGE LIFE- LONG MEASURES OF CVD RISK FACTORS AND TWO MIDLIFE MEASURES OF COGNITIVE FUNCTION IN THE FULL BOGALUSA HEART STUDY (BHS) COHORT (N=1,298; 850 WHITES AND 448 BLACKS), ALONG WITH AD-RELATED NEUROBIOLOGICAL SUBSTRATES FROM BRAIN MAGNETIC RESONANCE I