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Immune Cells in Alzheimer’s Disease and Related Dementias in the Jackson Heart Study

Award Number: R01AG075884
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Immune Cells in Alzheimer’s Disease and Related Dementias in the Jackson Heart Study - PROJECT SUMMARY Most older adults experience changes in immune system function which lead to chronic elevations in inflammation biomarkers. Chronic inflammation leads to elevated risk of many age-related disorders, including Alzheimer’s disease and related dementias (ADRD); however, the exact mechanisms remain unclear. There is a higher burden of both ADRD and chronic inflammation in African American populations, likely in large part due to social determinants of health (SDOH) and psychosocial stress. Pro-inflammatory innate and adaptive circulating immune cells, and inflammation related genes in these cell types, may be associated with an increased risk of mild cognitive impairment (MCI) and dementia among community-dwelling older African Americans. We propose to characterize the circulating proportions of monocytes, T and B cell, and innate lymphocytes (>50 cellular phenotypes) and gene expression in immune cells in ~1440 African American participants enrolled in the well-characterized population-based Jackson Heart Study, using samples collected and stored at the upcoming Exam 4 (2021-2023). We will then evaluate associations of immune cells and inflammation pathway gene expression with age, psychosocial stress and SDOH, plasma biomarkers of Alzheimer’s disease neuropathology, magnetic resonance imaging (MRI) based neurodegeneration and cerebrovascular disease measures, and MCI and dementia status. We will examine these relationships both cross-sectionally and longitudinally, using previously funded RNA-sequencing and immune phenotyping data at the Jackson Heart Study baseline exam, and assess differences by sex, given known sex differences in immune system function. We hypothesize that pro-inflammatory cell types and transcripts will be associated with MCI, dementia, and its risk factors and that inflammation may statistically mediate associations between higher psychosocial stress/SDOH burden and risk of MCI/dementia. We will also use data from immune cells to identify putative target genes and biological mechanisms for dementia risk variants, especially for variants more common in African versus European ancestry populations. This study is responsive to PAR-19-070 (NOT-AG-18-047: Health Disparities and Alzheimer’s Disease), as well as the January 2021 NIA approved concept calling for increased study of adaptive immunity in ADRD. It will add unique immune function and RNA sequencing data to one of the largest ongoing cohort studies of aging African American adults, with longitudinal phenotyping available since 2000. The generated data will be made widely available to the scientific community through appropriate public repositories (such as dbGaP) and can be used to address how immune cells and their gene expression influence risk of both dementia and other important disease outcomes in aging African Americans, cross-sectionally and longitudinally. Identification of specific and non-invasive inflammation biomarkers associated with MCI and dementia risk will improve understanding of disease biology and inform selection of putative anti-inflammatory therapeutics for ADRD.


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 = $735,074 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	4	3/5/2025	NON-COMPETING CONTINUATION	$675,068
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	001	4	6/17/2025	NON-COMPETING CONTINUATION	$60,006
														Subtotal = $735,074

Issue Date FY: 2024 ( Subtotal = $757,676 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	001	3	5/1/2024	NON-COMPETING CONTINUATION	$75,768
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	3	11/21/2023	NON-COMPETING CONTINUATION	$681,908
														Subtotal = $757,676

Issue Date FY: 2023 ( Subtotal = $782,288 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	2	1/19/2023	NON-COMPETING CONTINUATION	$782,288
														Subtotal = $782,288

Issue Date FY: 2022 ( Subtotal = $804,770 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	1	2/17/2022	NEW	$804,770
														Subtotal = $804,770

Grand Total All Awards = $3,079,808

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Immune Cells in Alzheimer’s Disease and Related Dementias in the Jackson Heart Study

Award Number: R01AG075884

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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