CONTRIBUTION OF HYPOCRETIN NEURON ACTIVITY TO ALZHEIMER'S RELATED SLEEP DISTURBANCES - PROJECT SUMMARY SLEE…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG086609_075
- FAIN
- R00AG086609
- Recipient
- THE REGENTS OF THE UNIVERSITY OF COLORADO
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $249,000
- Period
- Jul 1, 2026 – Mar 31, 2029
- Fiscal year
- 2026
- Place of performance state
- CO
- Source file
- FY2026_All_Assistance_Full_20261006.zip
Description
CONTRIBUTION OF HYPOCRETIN NEURON ACTIVITY TO ALZHEIMER'S RELATED SLEEP DISTURBANCES - PROJECT SUMMARY SLEEP IS A VERY WELL CONSERVED BEHAVIORAL STATE ACROSS ALL ANIMALS. THOUGH THE EXACT FUNCTION OF SLEEP REMAINS UNKNOWN, IT IS WIDELY APPRECIATED THAT GOOD SLEEP QUALITY IS A CORNERSTONE FOR ANY HEALTHY ORGANISM. INDEED, SEVERAL NEUROLOGICAL DISORDERS ARE CO-MORBID WITH SLEEP DISTURBANCES. FURTHERMORE, ALTERED SLEEP AS OBSERVED IN SLEEP APNEA, INSOMNIA OR SLEEP DEPRIVATION SHOW IMPAIRMENTS IN MEMORY CONSOLIDATION AND INCREASED RISK FOR DEPRESSION, CANCER, ALZHEIMERâS DISEASE (AD), AND OTHER NEUROPSYCHIATRIC DISORDERS. AD PATIENTS HAVE BEEN SHOWN TO DISPLAY ALTERED SLEEP ARCHITECTURE. SLEEP PLAYS A ROLE IN CLEARANCE OF BETA-AMYLOID (AÎ) IN INTERSTITIAL SPACE. EXCESSIVE ACCUMULATION OF AÎ, A PROMINENT FEATURE OF AD, HAS BEEN SHOWN TO ALTER SLEEP. RECENT WORK IN OUR LAB HAS DEMONSTRATED THAT HYPEREXCITABILITY OF WAKE-PROMOTING HYPOCRETIN (HCRT) NEURONS OF THE LATERAL HYPOTHALAMUS (LH), RESULTING FROM NATURAL AGING, MAY UNDERLIE INCREASED SLEEP FRAGMENTATION DURING AGING. IT IS LIKELY THAT THESE SAME NEURONS MAY HAVE ALTERED EXCITABILITY IN AD, EXACERBATED BY THE PRESENCE OF AÎ ACCUMULATION, AND MAY DRIVE SLEEP FRAGMENTATION AND SLEEP DISTURBANCES OBSERVED IN AD PATIENTS. THE OVERARCHING AIM OF THIS PROPOSAL IS TO UNDERSTAND HOW AÎ ACCUMULATION IMPACTS HYPOCRETIN NEURON ACTIVITY LEADING TO ALTERED HOMEOSTATIC SLEEP PRESSURE AND SUBSEQUENT DISRUPTED SLEEP ARCHITECTURE OBSERVED IN ALZHEIMERâS DISEASE. THE CENTRAL HYPOTHESIS IS THAT ACCUMULATION OF AÎ ACCELERATES NATURAL HCRT NEURON DEATH LEADING TO HYPEREXCITABILITY OF SURVIVING HCRT NEURONS AND DISRUPTED SLEEP PRESSURE AND ARCHITECTURE. THIS PROPOSAL FOCUSES ON HCRT NEURONS AS THEY HAVE BEEN SUGGESTED TO BE AN INTEGRATION HUB WHICH CONSOLIDATES SEVERAL STREAMS OF INPUT AND SENDS SIGNALS TO DOWNSTREAM AROUSAL-PROMOTING REGIONS. TO UNDERSTAND THIS INTERACTION, I WILL FIRST NEED TO DEMONSTRATE ALTERED HCRT NEURON A