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Mass spectrometry and multiplexed immunofluorescence imaging of metabolic and proteomic contributors to selective neuronal vulnerability in Alzheimer's disease

Award Number: R01AG078755
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Mass spectrometry and multiplexed immunofluorescence imaging of metabolic and proteomic contributors to selective neuronal vulnerability in Alzheimer's disease - We aim to uncover metabolic and protein signaling pathways contributing to the regional vulnerability of neocortical pyramidal neurons in Alzheimer's disease and to identify novel targets for detection and intervention. We will compare the prefrontal cortex, a neocortical brain area afflicted by neuropathology early in Alzheimer's disease, with the primary visual cortex, a brain area that is relatively spared. We will use mass spectrometric imaging in combination with segmentation analyses, to identify spatial changes of small molecules and proteins in postmortem brain sections prepared from these neocortical areas from donors at various clinical and pathological stages of Alzheimer's disease compared to controls. Then, we will apply multiplexed immunofluorescence imaging on sequential sections from the same specimens, to obtain information on cellular and microenvironment changes in and around vulnerable neocortical neurons during disease progression, correlated with the clinical severity, degree and location of neuropathological changes, and the risk genotype. Further, we will register the data from both imaging techniques to identify metabolic pathways and protein signaling changes at the regional, laminar and cellular level and to locate covariation in molecular and cellular phenotypes contributing to Alzheimer's disease vulnerability. In addition to generating a comprehensive dataset of the cellular and molecular changes at various stages of Alzheimer's disease, these studies will involve the development, validation, and dissemination of novel tools for analysis of large datasets generated using two powerful imaging tools, one that detects hundreds of analytes with the possibility of detecting previously unknown contributors to disease and the other that provides higher resolution with a select set of known markers. In the long term, the data generated from these studies could provide the basis for testing novel disease- modifying treatments by cell-type specific targeting of identified metabolic pathways using experimental models, such as brain organoids to replicate cortical lamination with human neurons or humanized mouse chimeras to model interactions between neurons and non-neuronal cell types.


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 = $807,254 )
2025	2025	UNIVERSITY OF RHODE ISLAND	75 LOWER COLLEGE RD RM 103	KINGSTON	RI	02881	WASHINGTON	USA	Aging Research	002	4	7/30/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$807,254
2025	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	3	7/30/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	3	7/30/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $807,254

Issue Date FY: 2024 ( Subtotal = $890,777 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	001	3	7/25/2024	SUPPLEMENT FOR EXPANSION	$71,342
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	3	5/31/2024	NON-COMPETING CONTINUATION	$819,435
														Subtotal = $890,777

Issue Date FY: 2023 ( Subtotal = $860,474 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	2	6/15/2023	NON-COMPETING CONTINUATION	$860,474
														Subtotal = $860,474

Issue Date FY: 2022 ( Subtotal = $880,858 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Aging Research	000	1	9/14/2022	NEW	$880,858
														Subtotal = $880,858

Grand Total All Awards = $3,439,363

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Mass spectrometry and multiplexed immunofluorescence imaging of metabolic and proteomic contributors to selective neuronal vulnerability in Alzheimer's disease

Award Number: R01AG078755

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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