# The impact of Alzheimers Disease neuropathology on immune cell senescence in older African Americans

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $232,792

## Abstract

Abstract
This administrative supplement proposal is submitted in response to NOSI NOT-AG-20-034 to add
Alzheimer’s-relevant studies to the PIs’ parent proposal “Causes of Immune Cell Senescence in Aging
Humans.” The parent grant was designed to test the hypothesis that aging causes various subsets of
human circulating immune cells to increasingly undergo telomere dysfunction-induced cellular
senescence with advancing age, thereby resulting in an age-associated dysregulation of immune cell
function. Preliminary data included in the original proposal revealed a dramatic and significant increase
in the percentages of senescent CD8+ T cells with advanced age, ranging from about 24% in people’s
20s to levels of about 65% by the time they reach their 60s, but with a range of senescent cells across
different donors. The active grant does not include any research questions relating to Alzheimer’s
Disease (AD). As such, without changing the aims of the parent grant, we seek supplemental funding for
additional methods and participant recruitment to address the possibility that, among the healthy older
participants recruited, some may have higher genetic risk for AD, and possibly be in the earliest stages
of preclinical AD, despite presenting with no readily-apparent cognitive deficits. This is a significant
concern because there is a growing appreciation that AD involves disruption to the immune system. To
address this possibility, we have entered into new collaborations with two teams of well-respected and
well-funded AD-researchers. With Mark Gluck at Rutgers University-Newark’s Aging & Brain Health
Alliance, we propose to recruit 32 additional African-American participants, ages 60 and above, from
their Pathways to Health Aging in African Americans cohort. The large size of Gluck’s existing cohort
allows us to pre-select those individuals with the highest and lowest APOE risk; half of these participants
will be pre-selected for high genetic risk for AD (APOE genotypes ε4ε4, ε3ε4), with the other half having
low genetic risk for AD (APOE genotypes ε2ε2, ε2ε3). We will also recruit an additional 16 African-
American individuals in their 20’s and 30’s as younger controls. A second new set of collaborators, Drs.
Blennow and Zetterberg, from the University of Gothenburg, are experts in blood-based biomarkers for
early AD; plasma will be sent to these Swedish collaborators where they will assess blood-based AD
biomarkers, including P-Tau181. We will carry out measurements of peripheral immune cell senescence
in these cohorts as described in the parent grant using flow cytometric, microscopic and genomic
analyses. We hypothesize that older participants (ages 60 and above) who are at high APOE-genetic
risk for AD will show enhanced levels of senescence in CD8+ T cells and will have enhanced
histochemical evidence of telomere dysfunction in their CD8+ T cells as compared to participants who
have low APOE-genetic risk for AD, and will have higher levels of P-Tau1...

## Key facts

- **NIH application ID:** 10287864
- **Project number:** 3R21AG067368-02S1
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** PATRICIA FITZGERALD-BOCARSLY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $232,792
- **Award type:** 3
- **Project period:** 2020-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287864

## Citation

> US National Institutes of Health, RePORTER application 10287864, The impact of Alzheimers Disease neuropathology on immune cell senescence in older African Americans (3R21AG067368-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10287864. Licensed CC0.

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