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Investigation of impaired neural stem cell activation in Alzheimer's Disease

Award Number: R01AG076933
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Investigation of impaired neural stem cell activation in Alzheimer's Disease - PROJECT SUMMARY Alzheimer’s Disease (AD) is a devastating neurodegenerative disease that causes severe atrophy in the hippocampal area. The dentate gyrus of the mammalian hippocampus harbors populations of quiescent neural stem cells (NSCs) that can re-enter the cell cycle and differentiate into functional excitatory neurons. This process of neurogenesis supports learning and memory functions, as well as healthy mood regulation. However, in aging and AD, levels of neurogenesis sharply decline, and work in rodents has demonstrated a functional link between levels of neurogenesis and cognitive performance. Although quiescent NSCs are the source of new neurons, the current understanding of how these cells are impacted in AD is extremely limited. Preliminary work shows that quiescent NSCs are defective in a mouse model of AD. Moreover, these cells are particularly vulnerable to damage during aging, which is the greatest risk factor for AD. This proposal takes an integrated, multiomics approach to address the critical question of how the quiescent pool is affected in AD. Using a well-established mouse model and human tissue, specific Aim 1 will define the transcriptomic and epigenomic changes at the single cell level in AD. Work in Aim 2 will employ metabolomics to fully elucidate the metabolic changes that occur in AD. Lastly, Aim 3 will use a functional transcriptomics screen targeting central pathways in quiescent NSCs to identify how these cells are selectively vulnerable in AD. Together this work will result in a comprehensive understanding of how dormant NSCs are affected in a mouse model of AD as well as in human tissue. This study will provide key data to the neurodegeneration community that can be leveraged for functional studies and the development of interventions to prevent, treat and even cure neurodegeneration in the long term.


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 = $0 )
2026	2025	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	000	4	3/27/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $472,287 )
2025	2025	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	001	4	6/18/2025	NON-COMPETING CONTINUATION	$38,554
2025	2025	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	000	4	3/14/2025	NON-COMPETING CONTINUATION	$433,733
														Subtotal = $472,287

Issue Date FY: 2024 ( Subtotal = $462,646 )
2024	2024	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	001	3	6/5/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$462,646
2024	2024	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	004	3	6/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$523,818
2024	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	2	5/31/2024	NON-COMPETING CONTINUATION	$0
2024	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	003	2	6/26/2024	NON-COMPETING CONTINUATION	-$404,090
2024	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	002	1	6/26/2024	NEW	-$119,728
														Subtotal = $462,646

Issue Date FY: 2023 ( Subtotal = $404,090 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	2	3/31/2023	NON-COMPETING CONTINUATION	$404,090
														Subtotal = $404,090

Issue Date FY: 2022 ( Subtotal = $409,100 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	1	5/19/2022	NEW	$409,100
														Subtotal = $409,100

Grand Total All Awards = $1,748,123

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Investigation of impaired neural stem cell activation in Alzheimer's Disease

Award Number: R01AG076933

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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