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Risk Factors, Pathology, and Clinical Expressions of AD

Award Number: R01AG015819
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/1998
PERIOD OF PERFORMANCE END DATE: 04/30/2027

Group Awards By:

View Award Description

Risk Factors, Pathology, and Clinical Expressions of AD - ABSTRACT Over the past project periods we tracked the biological basis of cognitive decline and dementia to understand the heterogeneous contributions of a dozen brain pathologies to individuals in the Religious Orders Study and Rush Memory and Aging Project (ROSMAP). We identified numerous genomic, medical, experiential, and psychological factors associated with cognitive decline and incident Alzheimer’s dementia, and also neurobiologic pathways linking some of these factors to Alzheimer’s disease (AD) and to related dementias. In the most recent funding period, to understand the biological basis of risk factors, we analyzed multi-region multi-omic data to identify novel and potentially high value therapeutic targets for the treatment and prevention of AD and related dementias. The computational biology target nominations were validated with targeted proteomics. All data are well-organized and shared publically with stakeholders around the globe. The overall goal of the proposed continuation is to identify additional protein targets, and their splice isoforms and post-translational modifications (PTMs) that drive AD related traits and can serve as novel therapeutic targets. We focus specifically on the hippocampus and entorhinal cortex, a region that is a key hub in the neurodegenerative disease network. Further, several neurodegenerative disease pathologies including tau tangles, TDP-43, Lewy bodies, and hippocampal sclerosis, are far more common in these regions relative to the neocortical regions with existing omic data. Aim 1 will generate bulk and single cell RNAseq and deep tandem mass tag (TMT) proteomics which can now generate upwards of 10,000 unique proteins making it virtually genome-wide; it will use these data to identify cell type-specific molecular systems, i.e., dozens to hundreds of coexpressed genes and proteins. Aim 2 will identify the specific molecular systems that drive AD related traits; further, through integration of all omic data from all regions it will identify key drivers of these systems. This will nominate genes and proteins that could serve as therapeutic targets. Aim 3 will perform top-down proteomics to identify splice isoforms, proteolytic fragments, and post-translational modifications of select high value proteins. Secondary aims will continue to explore the biologic pathways linking risk factors to AD related traits which has been the main deliverable of this grant since its inception; it will also share the newly generated data with the wider AD research community. The proposal will deliver high value therapeutic targets which will be passed to the Accelerated Medicines Partnership-AD (AMP-AD) consortium for further study. Thus, the identification of these proteins will have a high and sustained impact on the field of aging and dementia.


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	2024	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	21	3/19/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	21	5/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $2,868,751 )
2024	2024	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	21	5/24/2024	NON-COMPETING CONTINUATION	$2,868,751
														Subtotal = $2,868,751

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	20	7/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $2,950,095 )
2022	2022	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Aging Research	000	20	5/16/2022	NON-COMPETING CONTINUATION	$2,950,095
2022	2022	RUSH UNIVERSITY MEDICAL CENTER	1620 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Aging Research	001	20	5/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,950,095

Issue Date FY: 2021 ( Subtotal = $2,884,209 )
2021	2021	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	19	5/28/2021	NON-COMPETING CONTINUATION	$2,884,209
														Subtotal = $2,884,209

Issue Date FY: 2020 ( Subtotal = $2,603,054 )
2020	2020	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	18	4/20/2020	NON-COMPETING CONTINUATION	$2,603,054
														Subtotal = $2,603,054

Issue Date FY: 2019 ( Subtotal = $2,104,828 )
2019	2019	RUSH UNIVERSITY MEDICAL CENTER	1653 W CONGRESS PRKWY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	17	7/11/2019	COMPETING CONTINUATION	$2,104,828
														Subtotal = $2,104,828

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2013	RUSH UNIVERSITY MEDICAL CENTER	1653 WEST CONGRESS WAY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	15	9/19/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $713,280 )
2013	2013	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	15	6/7/2013	NON-COMPETING CONTINUATION	$713,280
														Subtotal = $713,280

Issue Date FY: 2012 ( Subtotal = $788,428 )
2012	2012	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	14	6/20/2012	NON-COMPETING CONTINUATION	$788,428
														Subtotal = $788,428

Issue Date FY: 2011 ( Subtotal = $0 )
2011	2010	RUSH-PRESBYTERIAN-ST LUKE`S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	13	7/29/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $793,219 )
2010	2010	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	13	6/15/2010	NON-COMPETING CONTINUATION	$793,219
														Subtotal = $793,219

Issue Date FY: 2009 ( Subtotal = $677,729 )
2009	2009	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	12	6/23/2009	NON-COMPETING CONTINUATION	$677,729
														Subtotal = $677,729

Issue Date FY: 2008 ( Subtotal = $693,242 )
2008	2008	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	11	8/12/2008	COMPETING CONTINUATION	$693,242
														Subtotal = $693,242

Issue Date FY: 2007 ( Subtotal = $599,328 )
2007	2007	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	10	6/29/2007	NON-COMPETING CONTINUATION	$599,328
														Subtotal = $599,328

Issue Date FY: 2006 ( Subtotal = $605,948 )
2006	2006	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	9	6/27/2006	NON-COMPETING CONTINUATION	$605,948
														Subtotal = $605,948

Issue Date FY: 2005 ( Subtotal = $617,805 )
2005	2005	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	8	5/25/2005	NON-COMPETING CONTINUATION	$617,805
														Subtotal = $617,805

Issue Date FY: 2004 ( Subtotal = $637,669 )
2004	2004	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	7	6/4/2004	NON-COMPETING CONTINUATION	$637,669
														Subtotal = $637,669

Issue Date FY: 2003 ( Subtotal = $655,038 )
2003	2003	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	6	8/25/2003	COMPETING CONTINUATION	$655,038
														Subtotal = $655,038

Issue Date FY: 2002 ( Subtotal = $394,801 )
2002	2002	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	5	6/17/2002	NON-COMPETING CONTINUATION	$394,801
														Subtotal = $394,801

Issue Date FY: 2001 ( Subtotal = $403,935 )
2001	2001	RUSH-PRESBYTERIAN-ST LUKE'S MEDICAL CENTER	1700 WEST VAN BUREN STREET	CHICAGO	IL	60612	COOK	USA	Aging Research	000	4	6/11/2001	NON-COMPETING CONTINUATION	$403,935
														Subtotal = $403,935

Issue Date FY: 2000 ( Subtotal = $442,948 )
2000	2000	RUSH UNIVERSITY MEDICAL CENTER	1653 WEST CONGRESS WAY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	3	8/18/2000	NON-COMPETING CONTINUATION	$442,948
														Subtotal = $442,948

Issue Date FY: 1999 ( Subtotal = $423,968 )
1999	1999	RUSH UNIVERSITY MEDICAL CENTER	1653 WEST CONGRESS WAY	CHICAGO	IL	60612	COOK	USA	Aging Research	001	2	8/10/1999	SUPPLEMENT FOR EXPANSION	$61,717
1999	1999	RUSH UNIVERSITY MEDICAL CENTER	1653 WEST CONGRESS WAY	CHICAGO	IL	60612	COOK	USA	Aging Research	000	2	6/3/1999	NON-COMPETING CONTINUATION	$362,251
														Subtotal = $423,968

Grand Total All Awards = $22,219,864

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Risk Factors, Pathology, and Clinical Expressions of AD

Award Number: R01AG015819

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/1998

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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