Wednesday, December 31, 2025 12/31/2025

Risk of Alzheimer's Disease and Related Dementias from Perinatal Lead Exposure: Brain Region and Cell Type Effects

Award Number: R01AG072396
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Risk of Alzheimer's Disease and Related Dementias from Perinatal Lead Exposure: Brain Region and Cell Type Effects - PROJECT SUMMARY The lifetime risk and population burden of Alzheimer’s disease and related dementias is high. Many dementias have a poorly characterized risk contribution from environmental factors. In longitudinal epidemiology studies, lead (Pb) exposure is linked to cognitive decline and Alzheimer’s disease. Despite public health efforts, Pb exposure remains widespread worldwide, with substantial exposure disparities. Early life is a particularly vulnerable exposure period. Using an established mouse model of perinatal Pb exposure, data from our research team suggests effects of Pb exposure persist into adulthood through epigenetic mechanisms, though epigenetic effects within brain regions over time have not been mapped. Brain region-specific analyses of genome-wide measures across multiple levels of the epigenome by perinatal Pb are critically needed. In addition, using single cell RNA-sequencing, our preliminary data demonstrate brain cell types have variable susceptibility to perinatal Pb exposure, specifically glial cells. Cell type-specific analyses of Pb exposure across time and brain region will establish cells particularly vulnerable to Pb exposure. We also showed Pb gene targets in the mouse overlap with key human dementia pathways. Further translation of toxicology to epidemiology findings is essential to maximize the advantages of both study designs. Together, our preliminary data support brain region and cell type specific alterations in epigenetic reprogramming and gene expression as likely targets of Pb exposure in the brain, which act on human relevant pathways, and highlight our team’s productivity and expertise in this area. The long-term goal of our research is to understand the sex-specific impacts of perinatal Pb exposure on brain composition and human dementia development. In a longitudinal study of mice perinatally exposed to Pb or control diet, we will test for Pb brain differences at multiple time points up to 18-months. We will 1) test how the effects of perinatal Pb exposure persist into adulthood by assaying pathological changes, behavior, RNA expression, DNA methylation, DNA hydroxymethylation, and chromatin conformation across three brain regions at three time points. We will 2) determine cell types in the brain most susceptible to the effects of Pb, using pathology and state-of-the-art ultrahigh resolution single cell spatial transcriptomics. We will 3) relate the molecular effects in mice from perinatal Pb exposure to existing data on human neurodegenerative disorders. This will be the first brain cell type specific map across multiple levels of the epigenome in response to a toxicant exposure. Using Pb as a model toxicant to identify molecular effects of perinatal exposure on brain regions and brain cell types, we will discover mechanistic insights into how environmental exposures drive dementia incidence with important toxicology, developmental biology, and public health implications.


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 = $686,633 )
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	000	5	12/17/2025	NON-COMPETING CONTINUATION	$686,633
														Subtotal = $686,633

Issue Date FY: 2025 ( Subtotal = $747,666 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	000	4	12/17/2024	NON-COMPETING CONTINUATION	$686,633
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	001	4	8/12/2025	NON-COMPETING CONTINUATION	$61,033
														Subtotal = $747,666

Issue Date FY: 2024 ( Subtotal = $757,235 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	001	3	5/22/2024	NON-COMPETING CONTINUATION	$75,724
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	000	3	11/30/2023	NON-COMPETING CONTINUATION	$681,511
														Subtotal = $757,235

Issue Date FY: 2023 ( Subtotal = $734,325 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	000	2	1/9/2023	NON-COMPETING CONTINUATION	$734,325
														Subtotal = $734,325

Issue Date FY: 2022 ( Subtotal = $734,325 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	000	1	2/11/2022	NEW	$734,325
														Subtotal = $734,325

Grand Total All Awards = $3,660,184

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Risk of Alzheimer's Disease and Related Dementias from Perinatal Lead Exposure: Brain Region and Cell Type Effects

Award Number: R01AG072396

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer