MIDLIFE OBESITY AND PREDIABETES TRIGGER LATER LIFE COGNITIVE DECLINE THROUGH CENTRAL NERVOUS SYSTEM INFLAMM…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG071667_075
- FAIN
- R00AG071667
- Recipient
- MICHIGAN STATE UNIVERSITY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $742,019
- Period
- Sep 1, 2024 – May 31, 2027
- Fiscal year
- 2024
- Place of performance state
- MI
- Source file
- FY2024_All_Assistance_Full_20261006.zip
Description
MIDLIFE OBESITY AND PREDIABETES TRIGGER LATER LIFE COGNITIVE DECLINE THROUGH CENTRAL NERVOUS SYSTEM INFLAMMAGING AND INNATE IMMUNE DYSREGULATION OF CGAS/STING - THE SIZE OF THE AGING POPULATION IS REACHING RECORD LEVELS WORLDWIDE, CAUSING A PARALLEL INCREASE IN THE NUMBER OF INDIVIDUALS WITH COGNITIVE IMPAIRMENT AND DEMENTIA, INCLUDING ALZHEIMERâS DISEASE AND ALZHEIMERâS DISEASE- RELATED DEMENTIAS (AD/ADRD). MULTIPLE FACTORS PREDISPOSE INDIVIDUALS TO THE DEVELOPMENT OF COGNITIVE IMPAIRMENT AND DEMENTIA, INCLUDING OBESITY, THE METABOLIC SYNDROME, PREDIABETES, AND DIABETES, WHOSE RATES ARE ALSO GROWING WORLDWIDE. WITH FEW TO NO AVAILABLE TREATMENTS, RESEARCH IS CRITICAL TO UNDERSTAND THE MECHANISMS BY WHICH THESE METABOLIC DYSFUNCTIONS PROMOTE COGNITIVE IMPAIRMENT AND AD/ADRD WITH AGING, ESPECIALLY DURING EARLY PHASES OF METABOLIC IMBALANCE, SUCH AS IN MIDLIFE OBESITY AND IN PREDIABETES BEFORE PROGRESSION TO FRANK DIABETES. INFLAMMATION IS A COMMON DENOMINATOR ACROSS AGING, OBESITY, PREDIABETES, DIABETES, AND COGNITIVE IMPAIRMENT, INCLUDING IN AD/ADRD. INFLAMMATORY MECHANISMS MAY PLAY A PARTICULARLY IMPORTANT ROLE BY PROMOTING EARLY OR INCREASED INFLAMMAGING, A CHRONIC LOW-GRADE INFLAMMATION. ONE PARTICULAR INNATE INFLAMMATORY MECHANISM THAT MAY BE CONTRIBUTING TO INFLAMMAGING IS THE DOUBLE-STRANDED DNA (DSDNA) SENSING CGAS/STING PATHWAY. CGAS/STING IS DYSREGULATED IN PERIPHERAL TISSUES IN OBESITY, THE METABOLIC SYNDROME, PREDIABETES, AND DIABETES. THIS PATHWAY RESPONDS TO CYTOSOLIC DSDNA FROM BACTERIA OR VIRUSES OR RELEASED AS A RESULT OF NUCLEAR OR MITOCHONDRIAL STRESS AND UPREGULATES PRO-INFLAMMATORY CYTOKINES. WE HYPOTHESIZE THAT DYSLIPIDEMIA AND INSULIN RESISTANCE DURING THE PROGRESSION OF OBESITY AND PREDIABETES TRIGGER INFLAMMATORY PATHWAYS, INCLUDING CGAS/STING, THAT EXACERBATE AND TRANSMIT INFLAMMATORY SIGNALS WITHIN THE CENTRAL NERVOUS SYSTEM (CNS). WE ALSO ANTICIPATE THAT AS THE PRIMARY IMMUNE CELLS OF THE CNS, MICROGLIA MEDIATE THIS INFLAMMATORY TRANSM