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The brain cholesterol interactome

Award Number: R03AG070428
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2023

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The brain cholesterol interactome - Abstract Both serum cholesterol levels and the cholesterol carrying protein ApoE have been implicated in the development of Alzheimer’s disease. Despite intensive research, there is not a consensus for why hypercholesterolemia and ApoE are risk factors. In the brain, the majority of cholesterol and ApoE are made by astrocytes. We will use a recently created cholesterol probe as a novel approach to investigate how ApoE isoform impacts trafficking of cholesterol out of the astrocyte and into the neuron. This probe contains a photoactivatable group which creates covalent bonds to adjacent proteins. In addition, it has a click-chemistry group which allows probe-protein complex purification for mass spectrometry analysis. We will add the cholesterol probe to astrocyte lines expressing each of the human ApoE isoforms. With this approach we will answer the questions: 1. What are the cholesterol-protein interactions within astrocyte-secreted ApoE particles and how are these interactions impacted by ApoE isoform? 2. What are the cholesterol-protein interactions in the neuron which can be linked to Alzheimer’s disease associated genes, and are these interactions in the neuron impacted by ApoE isoform? Using this approach, we believe we will identify how some known Alzheimer’s disease risk alleles are connected to cholesterol/ApoE, and identify proteins not previously implicated in Alzheimer’s disease that are modified by cholesterol and may be contributing to the development of the disease.


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: 2024 ( Subtotal = -$1,673 )
2024	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	2	11/29/2023	NON-COMPETING CONTINUATION	-$1,673
														Subtotal = -$1,673

Issue Date FY: 2022 ( Subtotal = $161,500 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	2	1/19/2022	NON-COMPETING CONTINUATION	$145,350
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	001	2	5/10/2022	NON-COMPETING CONTINUATION	$16,150
														Subtotal = $161,500

Issue Date FY: 2021 ( Subtotal = $161,500 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	001	1	5/24/2021	NEW	$0
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Aging Research	000	1	1/28/2021	NEW	$161,500
														Subtotal = $161,500

Grand Total All Awards = $321,327

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The brain cholesterol interactome

Award Number: R03AG070428

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2023

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