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Systems Genetics Analysis of Sex Differences in Alzheimer's Disease

Award Number: R01AG074012
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Systems Genetics Analysis of Sex Differences in Alzheimer's Disease - PROJECT SUMMARY Our proposed research aims to identify sex-specific genetic drivers of neuropathologic, cognitive, and metabolic phenotypes of Alzheimer’s disease by integrating longitudinal behavioral and molecular data from AD mice with genetic, genomic and clinical data from human cohorts. We will leverage a newly generated mouse population that incorporates high-risk familial AD (FAD) mutations on a genetically diverse background (BXD panel) to identify modifiers that contribute to AD resilience in this ‘humanized’ mouse population. In parallel, we will incorporate cutting-edge single-cell omic approachs to generate a molecular atlas of human brains from carriers of FAD mutations (in APP, PSEN1 and PSEN2) and non-carriers with sporadic AD. By combining and validating analyses in both mouse and human datasets, we expect to find molecular candidates that robustly contribute to sex-specific variation in symptoms of AD. We will further validate these candidates using unparalleled in vivo mouse technology to not only empircally assess their role in sex-specific mechanisms of disease, but also to evaluate sex X genotype X treatment interactions in a subset of candidates (i.e., Apoe) to inform more personalized therapeutic approaches. The approach we propose benefits from the enhanced discovery power and value of existing human genetics resources and novel, precision AD mouse models across multiple institutions to investigate the mechanisms of sex differences in AD.


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 = $1,131,658 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	000	5	6/23/2025	NON-COMPETING CONTINUATION	$1,131,658
														Subtotal = $1,131,658

Issue Date FY: 2024 ( Subtotal = $1,189,985 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	002	4	7/10/2024	NON-COMPETING CONTINUATION	$1,189,985
2024	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	001	3	11/17/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,028,965
2024	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	2	11/17/2023	NON-COMPETING CONTINUATION	-$1,028,965
														Subtotal = $1,189,985

Issue Date FY: 2023 ( Subtotal = $1,400,225 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	001	3	8/4/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,400,225
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	002	3	9/15/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	2	8/4/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,400,225

Issue Date FY: 2022 ( Subtotal = $1,235,110 )
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	2	8/4/2022	NON-COMPETING CONTINUATION	$1,235,110
														Subtotal = $1,235,110

Issue Date FY: 2021 ( Subtotal = $1,282,851 )
2021	2021	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	1	8/27/2021	NEW	$1,282,851
														Subtotal = $1,282,851

Grand Total All Awards = $6,239,829

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Systems Genetics Analysis of Sex Differences in Alzheimer's Disease

Award Number: R01AG074012

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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