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Epidemiologic Study of Neural Reserve and Neurobiology of Aging

Award Number: R01AG017917
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2001
PERIOD OF PERFORMANCE END DATE: 09/14/2026

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Epidemiologic Study of Neural Reserve and Neurobiology of Aging - PROJECT SUMMARY/ABSTRACT Extensive progress was made in the previous funding period of the Rush Memory and Aging Project (MAP). We 1) elucidated the neuropathologic basis of cognitive decline due to Alzheimer’s disease and related disorders (ADRD), 2) discovered genomic, experiential, psychological, and medical risk factors for ADRD clinical and pathologic traits including numerous risk factors for Alzheimer’s dementia with little to no relationship with ADRD brain pathologies, and 3) identified numerous potential novel therapeutic targets for cognitive decline, especially targets for cognitive decline not explained by common brain pathologies i.e., resilience. Here, the average person has average resilience and individuals can be more or less resilient. Resilience is a high value therapeutic target because if druggable it would offset the effects of any combination of brain pathologies. In this funding cycle, we propose to continue to follow MAP participants and conduct autopsies, and in this cycle, to obtain skin biopsies at autopsy to support a powerful new drug discovery program that integrates existing brain omics data with a new human cellular model of disease, i.e., skin derived fibroblast cultures induced into neuronal lines from persons with more or less resilience. We propose to: 1) define a robust and specific molecular signature of resilience in the human brain; 2) identify gene targets of resilience and establish human low-resilience cell models derived from MAP participants of known resilience; and 3) conduct drug discovery screens in the low-resilience models to identify compounds that increase resilience. These aims are supported by compelling preliminary work. An Exploratory Aim will continue to identify risk factors for ADRD clinical and pathologic traits leveraging the rich resource generated from the exposure data, repeated measures, and neuropathologic traits . All aims will examine sex as a biologic variable. A Secondary Aim will continue to share the unique and valuable resources generated by MAP including the to-be-generated fibroblast cell lines with the scientific community. Harnessing mechanisms of resilience to ADRD can slow down or prevent cognitive decline regardless of the presence and complexity of common brain pathologies. Therefore, the genes and compounds identified from our study will provide new therapeutic remedies to boost brain reserve in combating ADRD-related dementia. We believe that the proposed continuation will have a high and sustained impact on the field of aging and dementia research.


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	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	20	9/1/2026	NON-COMPETING CONTINUATION	$0
2026	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	20	3/19/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	20	5/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	20	5/30/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $2,989,007 )
2023	2023	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	20	8/1/2023	NON-COMPETING CONTINUATION	$2,989,007
														Subtotal = $2,989,007

Issue Date FY: 2022 ( Subtotal = $2,998,331 )
2022	2022	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Aging Research	000	19	7/27/2022	NON-COMPETING CONTINUATION	$2,998,331
														Subtotal = $2,998,331

Issue Date FY: 2021 ( Subtotal = $3,008,531 )
2021	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	18	6/29/2021	NON-COMPETING CONTINUATION	$3,008,531
														Subtotal = $3,008,531

Issue Date FY: 2020 ( Subtotal = $3,035,766 )
2020	2020	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	002	17	5/28/2020	NON-COMPETING CONTINUATION	$3,035,766
2020	2019	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	16	5/16/2020	COMPETING CONTINUATION	$429,450
2020	2018	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	15	5/16/2020	NON-COMPETING CONTINUATION	-$429,450
														Subtotal = $3,035,766

Issue Date FY: 2019 ( Subtotal = $2,825,827 )
2019	2019	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	16	9/14/2019	COMPETING CONTINUATION	$2,825,827
2019	2018	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	15	9/13/2019	NON-COMPETING CONTINUATION	$0
2019	2018	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	002	15	9/16/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,825,827

Issue Date FY: 2018 ( Subtotal = $1,952,898 )
2018	2018	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	15	5/31/2018	NON-COMPETING CONTINUATION	$0
2018	2018	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	15	4/16/2018	NON-COMPETING CONTINUATION	$1,952,898
														Subtotal = $1,952,898

Issue Date FY: 2017 ( Subtotal = $1,959,843 )
2017	2017	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	14	6/14/2017	NON-COMPETING CONTINUATION	$195,984
2017	2017	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	14	3/31/2017	NON-COMPETING CONTINUATION	$1,763,859
														Subtotal = $1,959,843

Issue Date FY: 2016 ( Subtotal = $2,096,988 )
2016	2016	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	13	4/19/2016	NON-COMPETING CONTINUATION	$2,096,988
														Subtotal = $2,096,988

Issue Date FY: 2015 ( Subtotal = $1,967,107 )
2015	2015	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	12	3/27/2015	NON-COMPETING CONTINUATION	$1,967,107
														Subtotal = $1,967,107

Issue Date FY: 2014 ( Subtotal = $2,203,944 )
2014	2014	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	002	11	7/31/2014	COMPETING CONTINUATION	$24,608
2014	2014	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	11	6/18/2014	COMPETING CONTINUATION	$2,024,341
2014	2014	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	001	11	6/30/2014	SUPPLEMENT FOR EXPANSION	$152,995
2014	2014	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	003	11	8/1/2014	SUPPLEMENT FOR EXPANSION	$2,000
														Subtotal = $2,203,944

Issue Date FY: 2013 ( Subtotal = $519,864 )
2013	2013	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	10	7/3/2013	SUPPLEMENT FOR EXPANSION	$519,864
2013	2013	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	001	10	9/13/2013	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $519,864

Issue Date FY: 2012 ( Subtotal = $1,684,096 )
2012	2012	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	10	6/25/2012	NON-COMPETING CONTINUATION	$1,684,096
														Subtotal = $1,684,096

Issue Date FY: 2011 ( Subtotal = $1,666,519 )
2011	2011	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	9	6/30/2011	NON-COMPETING CONTINUATION	$1,666,519
														Subtotal = $1,666,519

Issue Date FY: 2010 ( Subtotal = $1,663,638 )
2010	2010	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	8	6/7/2010	NON-COMPETING CONTINUATION	$1,663,638
														Subtotal = $1,663,638

Issue Date FY: 2009 ( Subtotal = $1,615,537 )
2009	2009	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	7	6/23/2009	NON-COMPETING CONTINUATION	$1,615,537
														Subtotal = $1,615,537

Issue Date FY: 2008 ( Subtotal = $1,607,814 )
2008	2008	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	6	6/19/2008	COMPETING CONTINUATION	$1,607,814
														Subtotal = $1,607,814

Issue Date FY: 2007 ( Subtotal = $591,782 ) (Continued on the next page)
Grand Total All Awards = $43,319,019

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Epidemiologic Study of Neural Reserve and Neurobiology of Aging

Award Number: R01AG017917

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2001

PERIOD OF PERFORMANCE END DATE: 09/14/2026

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