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Neuroprotective Effects of Vascular Endothelial Growth Factor in Alzheimer's Disease

Award Number: R01AG061518
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Neuroprotective Effects of Vascular Endothelial Growth Factor in Alzheimer's Disease - Abstract The Vascular Endothelial Growth Factor (VEGF) family of proteins has been implicated in protection against Alzheimer’s disease (AD) and includes exciting and emerging targets for intervention in Alzheimer’s disease and related dementias (ADRD). Research from our team and others has led to the nomination of FLT1 as a top target for intervention in the Agora platform. This renewal seeks to expand representation in the molecular characterization of the VEGF family while providing the cellular resolution needed to move this family toward therapeutic intervention. Our data suggest that there are clear and expected changes in endothelial cells for a number of protein targets, and that microglial cells are equally relevant for our top target FLT1. Unfortunately, both of these cell types are poorly represented in most single nucleus datasets, presenting a pressing need to expand our work to improve cellular resolution. This renewal will leverage advanced vascular isolation protocols and state-of-the-art spatial proteomic and transcriptomic techniques to provide unprecedented cellular resolution. Additionally, there is an opportunity to expand our analysis of this critical family of proteins to a cross-national brain bank to improve representation and ensure our findings generalize to the global population. The overarching goal of this work is to move multiple targets within the VEGF family of proteins toward therapeutic intervention leveraging deep molecular analysis in human brain. We hypothesize that VEGF effects rely on distinct ligand/receptor combinations that act in a cell-specific manner that can be pharmacologically manipulated. Uncovering the mechanism and cellular context of VEGF ligand/receptor combination associations with ADRD will provide selective targets for therapeutic intervention aimed at reducing the detrimental effects of the VEGF signaling malfunction. We are uniquely positioned to characterize the effects of VEGF using advanced multi-omic tools within three cohort studies from Rush University including the Pathology Alzheimer's and Related Dementias Study (PARDoS), a longitudinal cohort study in Brazil led by Rush. This renewal has the bold and important goal of expanding representation in molecular characterization of Alzheimer’s disease brains, while moving from molecular observation to nominated and well-characterized targets for intervention. The results of this work will provide a comprehensive characterization of each VEGF family member including the cellular context of effects, clinical stage at which intervention may be most beneficial, and a set of biomarker candidates that could facilitate participant identification and tracking for future interventions. All data will be shared in accordance with the open data science policies of the Accelerating Medicines Partnership AD project (AMP-AD), facilitating deep vascular characterization of the AD brain from groups around the world.


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 = $1,705,551 )
2026	2026	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	6	2/26/2026	COMPETING CONTINUATION	$1,705,551
														Subtotal = $1,705,551

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	5	5/5/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $807,979 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	5	1/5/2023	NON-COMPETING CONTINUATION	$807,979
														Subtotal = $807,979

Issue Date FY: 2022 ( Subtotal = $817,176 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	4	4/25/2022	NON-COMPETING CONTINUATION	$817,176
														Subtotal = $817,176

Issue Date FY: 2021 ( Subtotal = $837,506 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	3	3/2/2021	NON-COMPETING CONTINUATION	$837,506
														Subtotal = $837,506

Issue Date FY: 2020 ( Subtotal = $853,100 )
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	2	2/14/2020	NON-COMPETING CONTINUATION	$853,100
														Subtotal = $853,100

Issue Date FY: 2019 ( Subtotal = $900,827 )
2019	2019	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	1	3/1/2019	NEW	$900,827
														Subtotal = $900,827

Grand Total All Awards = $5,922,139

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Neuroprotective Effects of Vascular Endothelial Growth Factor in Alzheimer's Disease

Award Number: R01AG061518

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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