ELUCIDATING THE ROLE OF ENDOCRINE AGING AS A RISK FACTOR FOR ALZHEIMER'S DISEASE - PROJECT SUMMARY WOMEN CO…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_K00AG079790_075
- FAIN
- K00AG079790
- Recipient
- TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $228,481
- Period
- Sep 21, 2022 – Apr 30, 2028
- Fiscal year
- 2024
- Place of performance state
- PA
- Source file
- FY2024_All_Assistance_Full_20261006.zip
Description
ELUCIDATING THE ROLE OF ENDOCRINE AGING AS A RISK FACTOR FOR ALZHEIMER'S DISEASE - PROJECT SUMMARY WOMEN CONSTITUTE TWO-THIRDS OF THE ALZHEIMERâS DISEASE (AD) POPULATION. WHILE THE SEX-SPECIFIC BIOLOGICAL MECHANISMS UNDERLYING WOMENâS INCREASED PREVALENCE ARE UNCLEAR, ACCUMULATING EVIDENCE POINTS TO MENOPAUSE AS A NEUROLOGICAL TRANSITION STATE THAT MAY INFLUENCE AD RISK. OVER THE LAST QUARTER CENTURY, THE VAST MAJORITY OF BRAIN IMAGING STUDIES HAVE STUDIED THE NEURAL BASIS OF AGE-RELATED COGNITIVE DECLINE IN ADULTS AGED 65 AND OLDER. THIS CONVENTION OVERLOOKS ONE OF THE MOST SIGNIFICANT NEUROENDOCRINE CHANGES IN A WOMANâS LIFEâ THE TRANSITION TO MENOPAUSEâAND LEAVES A GAP IN OUR UNDERSTANDING OF THE AGING BRAIN DURING THE CRITICAL MIDLIFE YEARS. THE MENOPAUSAL TRANSITION IS MARKED BY A SWEEPING DECLINE IN THE PRODUCTION OF SEX HORMONESâUP TO 90% IN THE CASE OF 17B-ESTRADIOL AND PROGESTERONE. ANIMAL STUDIES PROVIDE POWERFUL EVIDENCE THAT ESTRADIOL AND PROGESTERONE PLAY A NEUROPROTECTIVE ROLE IN BRAIN REGIONS VULNERABLE TO NEURODEGENERATION, INCLUDING THE PREFRONTAL CORTEX AND MEDIAL TEMPORAL LOBES. HOWEVER, THE DEGREE TO WHICH FEMALE REPRODUCTIVE AGING LEADS TO CHANGES IN HUMAN BRAIN MORPHOLOGY, INTRINSIC BRAIN NETWORK CONNECTIVITY, AND SUSCEPTIBILITY TO INCREASED AD PREVALENCE REPRESENTS A SIGNIFICANT KNOWLEDGE GAP THAT HAS YET TO BE ADEQUATELY EXAMINED. THIS PROPOSAL WILL ESTABLISH WHETHER THE DECLINE IN SEX STEROID HORMONES OVER THE MENOPAUSAL TRANSITION RELATES TO VULNERABILITY IN BRAIN CIRCUITS IMPLICATED IN AD. IN THE F99 PHASE (AIM 1), I WILL PROBE THE EFFECTS OF REPRODUCTIVE AGING ON THE BRAIN IN HEALTHY WOMEN (N=90, AGES 45â55), INVESTIGATING THE ENDOCRINE BASIS OF NEURAL AGING IN MIDLIFE. THE WELL-CHARACTERIZED SAMPLE IS ENRICHED TO INCLUDE A BALANCED DISTRIBUTION OF PRE, PERI, AND POST-MENOPAUSAL WOMEN ACROSS A LIMITED AGE RANGE IN ORDER TO ISOLATE THE EFFECTS OF REPRODUCTIVE AGING FROM CHRONOLOGICAL AGING. I WILL FIRST DETERMINE HOW THE DEPL