Thursday, January 1, 2026 1/1/2026

Statistical methods for population-level cell-type-specific analyses of tissue omics data for Alzheimer's disease

Award Number: R01AG080590
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Statistical methods for population-level cell-type-specific analyses of tissue omics data for Alzheimer's disease - PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) accounts for 60-80% of dementia cases and causes progressive neurodegeneration that ultimately leads to death. While the number of US people with late-onset AD is expected to reach 13.8 million by 2050, its prevention and treatment remain only modestly effective. Many efforts have been made to study AD pathophysiology by collecting and curating rich omics data from AD-affected or unaffected human brains, e.g., the National Institute on Aging's Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) project. Most of those omics data, such as gene expression, DNA methylation, and proteomics, are collected at the tissue level, and thus the cell-type-specific (CTS) signals are masked. Recently, with the emerging single-cell techniques, single-cell RNA-seq and DNA methylation data have been generated. However, given the difficulty of quantifying a small number of molecules and associated high costs, single-cell data suffer from high technical variation and are constrained to a small number of samples that lack representativity. To address these issues in AD research and accelerate our understanding of cellular multi-omics mechanisms underlying AD, we aim to: 1) Improve estimation of cellular fractions in brain tissue samples by the ensemble over existing methods and considering cell-type hierarchy. 2) Identify CTS differentially methylated regions (DMR) associated with AD. We will consider the spatial correlation of CpG sites and cell-type specificity. 3) We will further build statistical models to systematically integrate those CTS omics estimates via omics-wide association studies and causal mediation analyses. Through extensive analyses of several large cohorts in AMP-AD datasets, we will produce statistically significant and biologically meaningful omics results at an unprecedented population-scale and cell-type resolution, which will improve our understanding of complex AD biology. We will validate our findings using additional data available within and outside the AMP-AD project, including single-cell multi-omics data. The resulting methods will be implemented as efficient computational algorithms via public software readily available to the research community. Successful completion of this project will provide state-of-the-art methods for cell- type deconvolution and integrative multi-omics analyses and advance our knowledge of genes/proteins contributing to AD in selectively vulnerable brain regions and 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: 2026 ( Subtotal = $340,493 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	000	4	12/3/2025	NON-COMPETING CONTINUATION	$340,493
														Subtotal = $340,493

Issue Date FY: 2025 ( Subtotal = $370,759 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	000	3	11/14/2024	NON-COMPETING CONTINUATION	$340,493
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	001	3	1/14/2025	NON-COMPETING CONTINUATION	$0
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	002	3	9/23/2025	NON-COMPETING CONTINUATION	$30,266
														Subtotal = $370,759

Issue Date FY: 2024 ( Subtotal = $378,325 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	001	2	4/30/2024	NON-COMPETING CONTINUATION	$37,832
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	000	2	11/20/2023	NON-COMPETING CONTINUATION	$340,493
														Subtotal = $378,325

Issue Date FY: 2023 ( Subtotal = $378,325 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Aging Research	000	1	1/30/2023	NEW	$378,325
														Subtotal = $378,325

Grand Total All Awards = $1,467,902

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Statistical methods for population-level cell-type-specific analyses of tissue omics data for Alzheimer's disease

Award Number: R01AG080590

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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