SELECTIVE VULNERABILITY OF CELL TYPES IN BRAIN AGING AND ALZHEIMER'S DISEASE - PROJECT SUMMARY MAJOR HALLMA…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_K00AG083292_075
- FAIN
- K00AG083292
- Recipient
- UNIVERSITY OF WASHINGTON
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $143,356
- Period
- Sep 15, 2023 – May 31, 2029
- Fiscal year
- 2025
- Place of performance state
- WA
- Source file
- FY2025_All_Assistance_Full_20261006.zip
Description
SELECTIVE VULNERABILITY OF CELL TYPES IN BRAIN AGING AND ALZHEIMER'S DISEASE - PROJECT SUMMARY MAJOR HALLMARKS OF AGING AND NEURODEGENERATION INCLUDE COGNITIVE DECLINE, ALTERED BODY COMPOSITION, DYSREGULATION OF CIRCADIAN RHYTHMS, AND CHANGES IN NEUROENDOCRINE SYSTEMS. THE HYPOTHALAMUS IS THE BRAIN REGION THAT HARBORS A DIVERSITY OF NEURONAL SUBTYPES THAT COORDINATE THESE IMPORTANT FUNCTIONS. YET, THE EXTENT TO WHICH CHANGES IN THE HYPOTHALAMUS UNDERLIE FUNCTIONAL DECLINE IN NORMAL AGING AND NEURODEGENERATION IS NOT WELL UNDERSTOOD. INTRIGUINGLY, INTERVENTIONS TARGETING THE HYPOTHALAMUS CAN SIGNIFICANTLY EXTEND LIFESPAN IN MICE, WITH A DISCREPANCY IN FEMALES VERSUS MALES. MOREOVER, ALTERATIONS IN SLEEP AND BODY WEIGHT CAN OCCUR PRIOR TO THE ONSET OF NEURODEGENERATION, FOR EXAMPLE IN ALZHEIMERâS DISEASE (AD). ONE CHALLENGE IN UNDERSTANDING THE AGING PROCESS IS THAT IT IS HIGHLY HETEROGENEOUS, MEANING THAT DIFFERENT CELL-TYPES AGE DIFFERENTLY. FOR EXAMPLE, IN BRAIN AGING, WITHIN INDIVIDUALS, THE IMMUNE CELLS (MICROGLIA) AGE VERY DIFFERENTLY FROM NEURONS. MOREOVER, ACROSS INDIVIDUALS, WOMEN ARE MORE SUSCEPTIBLE TO AGE-ASSOCIATED NEURODEGENERATIVE DISEASES SUCH AS ALZHEIMERâS DISEASE (AD) THAN MEN. HOWEVER, THE SELECTIVE VULNERABILITY OF DIFFERENT CELL-TYPES IN THE BRAIN IN AGING AND AD, AND THE CELL-TYPE SPECIFIC MECHANISM UNDERLYING FEMALE BIAS IN BRAIN AGING ARE LARGELY UNKNOWN. FOR THE F99 PHASE OF THIS PROPOSAL, IN DR. WEBBâS LABORATORY AT BROWN UNIVERSITY, I WILL BUILD ON MY FOUNDATIONAL WORK IN WHICH I DEFINED THE CELL-TYPE TRANSCRIPTIONAL CHANGES THAT OCCUR IN THE AGING FEMALE MOUSE HYPOTHALAMUS. I WILL PERFORM MACHINE LEARNING ANALYSIS TO IDENTIFY SIGNATURES OF CELL VULNERABILITY AND RESILIENCE WITH AGE AND EXTEND THIS WORK TO A MODEL OF NEURODEGENERATION (AD MOUSE MODELS AND HUMAN POST-MORTEM TISSUE). UNDERSTANDING THE SELECTIVE VULNERABILITY IN AGING AND AD CAN HELP DEVELOP PRECISE INTERVENTIONS TO SPECIFICALLY TARGET THE VULNERABLE NEURONS TO SLOW DO