Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Dec 1;20(12):3529-3530.
doi: 10.4103/NRR.NRR-D-24-00793. Epub 2024 Oct 22.

Alzheimer's disease and the immune system: the emerging role of TEMRA cells

Edric D Winford  1 , Adam D Bachstetter  2
Affiliations

Alzheimer's disease and the immune system: the emerging role of TEMRA cells

Edric D Winford et al. Neural Regen Res. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Hypotheses on the role of T cells in Alzheimer’s disease. This figure illustrates three hypotheses explaining the relationship between T cells, infection, inflammation, and Alzheimer’s disease. (A) The viral reactivation and T cell exhaustion hypothesis proposes that strong T cell function controls chronic pathogens (e.g., CMV and EBV), while weakened function (increased TEMRA cells, decreased T diversity) leads to pathogen reactivation. These triggers increased IFNγ production and innate immune responses, potentially causing neuroinflammation, neurodegeneration, and Aβ accumulation. (B) The dysfunctional T cell activation hypothesis suggests T cell dysfunction increases chemokine production and T cell brain recruitment, resulting in neuroinflammation and neurodegeneration, possibly driven by tau pathology. (C) The susceptibility to infection hypothesis posits that neuroinflammation triggers the release of immune modulators (e.g., glucocorticoids, acetylcholine, and cytokines), weakening T cell function (e.g., increased TEMRA cells, decreased cytokines, and reduced barrier protection). This weakened state increases susceptibility to severe infections, leading to recurring systemic inflammation, delirium, and further neuroinflammation. These infections, in turn, further impair T cell function, creating a self-perpetuating cycle of T cell exhaustion and increased vulnerability to infections. Created with BioRender.com. ↑ Indicates increase or upregulation; ↓ indicates decrease or downregulation. Aβ: Amyloid-beta; CMV: cytomegalovirus; EBV: Epstein-Barr virus; IFNγ: interferon gamma; TEMRA: T effector memory cells re-expressing CD45RA.
See this image and copyright information in PMC

References

    1. Bachstetter AD, Lutshumba J, Winford E, Abner EL, Martin BJ, Harp JP, Van Eldik LJ, Schmitt FA, Wilcock DM, Stowe AM, Jicha GA, Nikolajczyk BS. A blunted T(H)17 cytokine signature in women with mild cognitive impairment: insights from inflammatory profiling of a community-based cohort of older adults. Brain Commun. 2023;5:fcad259. - PMC - PubMed
    1. Chen X, Firulyova M, Manis M, Herz J, Smirnov I, Aladyeva E, Wang C, Bao X, Finn MB, Hu H, Shchukina I, Kim MW, Yuede CM, Kipnis J, Artyomov MN, Ulrich JD, Holtzman DM. Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. Nature. 2023;615:668–677. - PMC - PubMed
    1. Deecke L, Homann J, Goldeck D, Ohlei O, Dobricic V, Drewelies J, Demuth I, Pawelec G, Bertram L, Lill CM. No increase of CD8+ TEMRA cells in the blood of healthy adults at high genetic risk of Alzheimer’s disease. Alzheimers Dement. 2024;20:3116–3118. - PMC - PubMed
    1. Gate D, et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature. 2020;577:399–404. - PMC - PubMed
    1. Gericke C, Kirabali T, Flury R, Mallone A, Rickenbach C, Kulic L, Tosevski V, Hock C, Nitsch RM, Treyer V, Ferretti MT, Gietl A. Early beta-amyloid accumulation in the brain is associated with peripheral T cell alterations. Alzheimers Dement. 2023;19:5642–5662. - PubMed

LinkOut - more resources