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ApoE and Heparan Sulfate Interaction in Alzheimer’s Disease

Award Number: R01AG087305
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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ApoE and Heparan Sulfate Interaction in Alzheimer’s Disease - Project Summary Polymorphism in the APOE gene is the leading risk modulator for late onset Alzheimer’s Disease (LOAD). Despite extensive studies, the molecular mechanisms by which Apolipoprotein E (ApoE) influences AD risk remain poorly understood. A growing body of research is pointing towards a significant role for ApoE/heparan sulfate interactions in AD pathogenesis. Heparan sulfate (HS) is ubiquitously present on neuronal and glial surface and facilitates ApoE cell surface binding and cellular uptake. In our recent studies, we have shown that ApoE/HS binding affinity correlates with AD risk and that ApoE recognizes a rare HS modification, 3-O-sulfation. In addition, we demonstrate an increase in the 3-O-sulfated HS in AD brains. In preliminary data, we show that ApoE4 allele further increases the level of 3-O-sulfated HS, leading to differential interaction between ApoE isoforms and HS in the brain. We hypothesize that the differential binding modes between ApoE isoforms and HS contribute to AD risk. This hypothesis will be tested on multiple levels using an interdisciplinary approach in three aims. Aim 1, Delineate the glycan determinants of ApoE-HS interaction in AD. Aim 2, Define isoform specific ApoE-HS interaction at atomic resolution. Aim 3, Study isoform specific ApoE-HS interaction in cellular and animal models. Successful completion of this project will provide novel insights into how ApoE isoforms modulate AD risk through their distinct interactions with HS, and will identify new drug targets for 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 = $732,702 )
2025	2025	RENSSELAER POLYTECHNIC INSTITUTE	110 8TH ST	TROY	NY	12180	RENSSELAER	USA	Aging Research	000	2	3/27/2025	NON-COMPETING CONTINUATION	$672,889
2025	2025	RENSSELAER POLYTECHNIC INSTITUTE	110 8TH ST	TROY	NY	12180	RENSSELAER	USA	Aging Research	001	2	6/13/2025	NON-COMPETING CONTINUATION	$59,813
														Subtotal = $732,702

Issue Date FY: 2024 ( Subtotal = $782,087 )
2024	2024	RENSSELAER POLYTECHNIC INSTITUTE	110 8TH ST	TROY	NY	12180	RENSSELAER	USA	Aging Research	000	1	5/3/2024	NEW	$782,087
														Subtotal = $782,087

Grand Total All Awards = $1,514,789

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ApoE and Heparan Sulfate Interaction in Alzheimer’s Disease

Award Number: R01AG087305

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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