# Cutaneous Pathogen-Specific Tissue Resident Memory T Cells in Human Aging

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $396,241

## Abstract

Project Summary
Several lines of evidence link infections to the pathogenesis of Alzheimer’s disease (AD). This
one-year Supplement application focuses on the potential role of HSV-1 infection. About 70% of
older adults are HSV-1 infected. The parent R01 concerns the viral pathogen VZV, shingles,
and aging, and is eligible for the Supplement as does not concern Alzheimer’s Disease. The
Supplement is related to the parent R01 because HSV-1 has a similar pathogenesis, sequence,
and antigenic structure to VZV, and also because aging is a risk factor for both shingles and
Alzheimer’s Disease.
The Supplement Premise is that the fine specificity of T cells recovered from anatomically and
clinically relevant specimens from Mild Cognitive Impairment (MCI) and Alzheimer’s Disease
subjects can be used as a biomarker probe possible microbial driver of these disorders.
Linkages between HSV-1 and AD include epidemiologic association of AD with HSV-1
seropositivity in APOE4(+) persons, detection of HSV-1 from AD tissues, the ability of HSV-1 to
trigger amyloidogenesis in vitro, and interactions between HSV-1 cerebral infection, human
APOE genotype, and dementia-like phenotypes in murine models.
The Investigative team includes experts in HSV-1 T cell biology, single cell T cell receptor
sequencing (scTCRseq) and TCR bioinformatic analysis, advanced histologic of human nervous
system tissue, and the clinical study of Mild Cognitive Impairment subjects. The study is home-
based at the University of Washington (UW) including the Alzheimer’s Disease Research Center
(ADRC), with one domestic and one international collaborative site. Importantly, ongoing NIH
grant/subcontract relationships exist between UW and each site and the PI has published
multiple recent papers with the Co-Investigators at each site.
Aim 1 recovers CSF and matched blood from HSV-1-seropositive persons with MCI and uses
wet-lab and TCRseq dry/wet methods to determine if HSV-1-specific T cells are enriched in
CSF compared to blood. Aim 2 recovers single T cells from curated AD autopsy tissues from
the Netherlands Brain Bank and similarly measures HSV-1 specificity. Together, the Aims
leverage the extreme sensitivity and memory characteristics of T cell immunity to examine the
hypothesis that HSV-1 is involved in Alzheimer’s Disease

## Key facts

- **NIH application ID:** 10118463
- **Project number:** 3R01AG064800-02S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** David M Koelle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,241
- **Award type:** 3
- **Project period:** 2019-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118463

## Citation

> US National Institutes of Health, RePORTER application 10118463, Cutaneous Pathogen-Specific Tissue Resident Memory T Cells in Human Aging (3R01AG064800-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10118463. Licensed CC0.

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