INFLUENCE OF GUT ON METABOLISM AND COGNITION IN ALZHEIMER'S DISEASE. - PROJECT SUMMARY: ALZHEIMERâS DISEA…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
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ASST_NON_R00AG078402_075 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · Department of Health and Human Services
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- Assistance award identifier
- ASST_NON_R00AG078402_075
- FAIN
- R00AG078402
- Recipient
- UNIVERSITY OF ALABAMA AT BIRMINGHAM
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $769,285
- Period
- Sep 1, 2022 – Jul 31, 2026
- Fiscal year
- 2023
- Place of performance state
- AL
- Source file
- FY2023_All_Assistance_Full_20261006.zip
Description
INFLUENCE OF GUT ON METABOLISM AND COGNITION IN ALZHEIMER'S DISEASE. - PROJECT SUMMARY: ALZHEIMERâS DISEASE (AD) IS THE MOST COMMON CAUSE OF DEMENTIA AND THE THIRD LEADING CAUSE OF DEATH IN OLDER ADULTS. IN ADDITION TO COGNITIVE IMPAIRMENT, AD IS ASSOCIATED WITH NEUROPATHOLOGY, IMPAIRED METABOLIC FUNCTION AND GUT MICROBIOME DYSBIOSIS. HOWEVER, THE RELATIONSHIPS BETWEEN GUT HEALTH (INCLUDING THE GUT MICROBIOME), METABOLISM AND COGNITIVE DECLINE REMAINS LARGELY UNKNOWN, DESPITE STRONG EVIDENCE THAT THE GUT-BRAIN-AXIS IS AN IMPORTANT INTERMEDIARY IN NEURODEGENERATIVE DISEASE. MOREOVER, NORMAL AGING ALSO INFLUENCES BOTH GUT MICROBIOME COMPOSITION AND PERIPHERAL METABOLIC HEALTH, DEMONSTRATING THE IMPORTANCE OF INCLUDING GEROSCIENCE AS A FACTOR. GUT DYSBIOSIS CAN RESULT IN IMPAIRED INSULIN RESISTANCE AS WELL AS OBESITY, BOTH OF WHICH INCREASE THE RISK OF DEVELOPING AD. THEREFORE, THE LONG TERM GOAL OF THIS PROJECT IS TO ELUCIDATE HOW ALTERED GUT MICROBIOME COMPOSITION CAN INFLUENCE COGNITIVE OUTCOMES IN AN AGED RAT MODEL OF AD TO IDENTIFY POTENTIAL TARGETS FOR THERAPEUTIC INTERVENTION. THE OVERALL OBJECTIVE IS TO INVESTIGATE WHETHER THE GUT IS ABLE TO EXERT ITS INFLUENCE OVER COGNITION THROUGH METABOLIC INTERMEDIATES, AS THE GUT MICROBIOME DIRECTLY INFLUENCES METABOLITE PRODUCTION AND ENERGY HOMEOSTASIS. THE RATIONALE FOR THIS PROJECT IS THAT VERY FEW, IF ANY, STRATEGIES DIRECTLY TARGETING BRAIN FUNCTION HAVE BEEN ABLE TO PREVENT OR DELAY COGNITIVE IMPAIRMENT WITH AD TO DATE. THIS LINE OF INVESTIGATION IS INNOVATIVE IN THAT IT SUGGESTS A PERIPHERAL TARGET, RATHER THAN TARGETING THE BRAIN DIRECTLY, FOR THE ALLEVIATION OF COGNITIVE SYMPTOMS BY UTILIZING THE STRONG, RECIPROCAL LINK BETWEEN GUT AND BRAIN FUNCTION. OUR PRELIMINARY DATA INDICATES THE TGF344-AD RAT MODEL MIMICS THE COGNITIVE DECLINE OBSERVED WITH AD, AS WELL AS THE PERIPHERAL METABOLIC IMPAIRMENTS AND GUT DYSBIOSIS ASSOCIATED AD. THE PROPOSED EXPERIMENTS WILL BUILD ON THESE FINDINGS AND TEST THE CENTRAL HYPOT