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3D Brain Tissue System for Modeling Resilience to Alzheimer's Disease and Drug Discovery

Award Number: R21AG075496
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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3D Brain Tissue System for Modeling Resilience to Alzheimer's Disease and Drug Discovery - PROJECT SUMMARY/ABSTRACT An alternative approach to discovering the causes of Alzheimer’s disease (AD) for the purposes of prevention, diagnosis, and treatment is to research individuals who remain cognitively healthy despite significant genetic risk or pathological burden, a phenomenon termed cognitive resilience. Our quest to understand the nature of cognitive resilience to normal aging and AD in the first genetically diverse AD mouse population (the AD-BXDs) that models the genetic, transcriptomic, and phenotypic heterogeneity of human late-onset AD yielded novel targets for resilience-based therapeutics. To rapidly identify compounds that will likely promote cognitive resilience in preclinical studies (in vivo) and beyond, there is a critical need for a system that recapitulates the key features of the AD brain including morphology, cell-cell interactions, and neural network functions in a dish (in vitro). We propose to develop a 3D co-culture system with neurons, astrocytes, and microglia that exploits established differences in the onset and progression of cognitive symptoms in the AD-BXDs to investigate cellular resilience to AD and validate this system for future discovery of novel resilience-based therapeutics. Notably, the translational relevance of compounds will be critically evaluated in vivo and by cross-species analyses that we and others developed using a variety of genetic, omics and clinical data. Our long-term goal is to develop personalized in vitro 3D assays to study, quantitatively and mechanistically, how aging changes cellular resiliency across a broad range of neuropathologies to develop novel, targeted interventions to enhance cognitive health across a broad spectrum of neurodegenerative diseases for diverse populations, leveraging our partnerships with pharmaceutical companies such as Icagen.


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: 2025 ( Subtotal = $0 )
2025	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	000	2	7/23/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	001	2	11/15/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$228,216
2024	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	1	11/15/2023	NEW	-$228,216
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $195,000 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	001	2	6/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$195,000
2023	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	1	6/22/2023	NEW	$0
														Subtotal = $195,000

Issue Date FY: 2022 ( Subtotal = $259,650 )
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	1	6/17/2022	NEW	$259,650
														Subtotal = $259,650

Grand Total All Awards = $454,650

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3D Brain Tissue System for Modeling Resilience to Alzheimer's Disease and Drug Discovery

Award Number: R21AG075496

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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