BRIEF RESEARCH REPORT article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
This article is part of the Research TopicNeuro-immune interaction in diseaseView all 4 articles
Single-Nucleus RNA-seq Reveals No Increase in T Cells in Alzheimer's Disease Prefrontal Cortex or Hippocampus
Provisionally accepted
- 1University of California San Francisco Memory and Aging Center, San Francisco, United States
- 2Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, San Francisco, United States
- 3Center for Alzheimer’s and Related Dementias, National Institutes of Health, Bethesda, MD 20892, United States
- 4DataTecnica LLC, Washington, DC 20037, United States
- 5University of California San Francisco Department of Radiology & Biomedical Imaging, San Francisco, United States
- 6Global Brain Health Institute, San Francisco, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Alzheimer's disease (AD) has long been associated with hallmark protein aggregates, yet increasing evidence suggests immune involvement may contribute to its progression. Prior studies have found increased T cell presence in AD brain tissue, raising the possibility of neuroimmune crosstalk. Methods: We used single-nucleus RNA sequencing data from the Religious Orders Study and Memory and Aging Project (ROSMAP), the largest available postmortem AD cohort, to investigate T cell dynamics in prefrontal cortex (PFC) and hippocampus. Results: Contrary to prior findings, we observed no significant increase in T cell frequency in individuals with pathologically confirmed AD in either region. We replicated these findings in dorsolateral PFC (DLPFC) using the Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Notably, although we confirmed a prior finding of T cell expansion in middle temporal gyrus (MTG), the strength of this association was affected by donor age. Additionally, we detected no change in gene expression in T cells in the brain parenchyma from individuals with AD. Impact: These results suggest that T cell enrichment in AD may be regionally restricted and not as widespread as previously assumed. Our findings underscore the importance of brain region selection, analytical approach, and dataset composition in interpreting immune cell dynamics in neurodegenerative disease.
Keywords: CD8 T cells, Alzheimer's disease, single-nucleus RNA sequencing, ROSMAP, Prefrontal Cortex
Received: 08 Aug 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Oxendine, Sirkis, Jonson and Yokoyama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jennifer S. Yokoyama, jennifer.yokoyama@ucsf.edu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.