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The role of astrocytes in TRN dysfunction and sleep disruption in Alzheimer's disease

Award Number: F31AG091930
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/14/2026
PERIOD OF PERFORMANCE END DATE: 09/13/2029

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The role of astrocytes in TRN dysfunction and sleep disruption in Alzheimer's disease - PROJECT SUMMARY/ABSTRACT The occurrence of age-related illnesses such as Alzheimer's disease (AD) is globally on the rise. Yet, effective strategies to treat or alleviate its devastating consequences are still lacking. This is due to the fact that significant pathological changes in the brain have already occurred by the time individuals are diagnosed with mild cognitive impairment or AD and start receiving treatment. Therefore, earlier intervention strategies are needed. AD is characterized by the pathological buildup of amyloid beta (A) and tau proteins leading to changes in cognition, behavior, and personality. Recent insights into the initial stages of AD progression suggest that deficits in sleep maintenance and slow wave sleep (SWS) can impact A production and clearance thereby leading to negative AD outcomes. Our lab has identified that hypofunctioning of the thalamic reticular nucleus (TRN) plays a significant role in sleep maintenance and SWS deficits in the J20 mouse model of AD which over express mutant human amyloid precursor protein (APP). However, currently there is no consensus on the mechanisms responsible for the disruption of TRN function. Astrocytes play crucial roles in brain function and disease processes, such as immune responses, blood-brain barrier maintenance, metabolic support for neurons, regulating synaptic activity, and maintaining synaptic connections. In AD, astrocytes undergo genetic, morphological, and functional changes that can disrupt neuronal function making them likely contributors to TRN dysfunction. Preliminary data from our lab demonstrate that astrocytes in the TRN of APP mice also exhibit gene expression differences and morphological alterations that begin in the earliest phases of disease progression. Therefore, to further investigate the role astrocytes play in AD related thalamocortical dysfunction and subsequent sleep disturbances I will 1) Characterize morphological alterations in TRN astrocytes across AD disease progression and their impact on TRN function. 2) Over express genes related to astrocyte morphology in the TRN of APP mice to normalize astrocyte morphology and function, with consequences on TRN activity, sleep, and disease progression. Together, this work will be critical in advancing our understanding of the complex relationship between sleep, astrocytes, and AD, and may pave the way for new therapies to slow or halt the progression of this devastating disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Aging Research	000	1	9/14/2026	NEW	$50,114
2026	2026	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Aging Research	001	1	9/14/2026	NEW	$0
														Subtotal = $50,114

Grand Total All Awards = $50,114

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The role of astrocytes in TRN dysfunction and sleep disruption in Alzheimer's disease

Award Number: F31AG091930

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/14/2026

PERIOD OF PERFORMANCE END DATE: 09/13/2029

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