New Perspective: Bench to Bedside Evidence of the Role of CD8+ T Cells in Alzheimer's Disease

TL;DR

This paper explores the role of CD8+ T cells in Alzheimer's disease, suggesting they may offer new therapeutic strategies beyond traditional targets like amyloid-beta and tau.

Contribution

Highlights the previously underappreciated role of CD8+ T cells in Alzheimer's disease and their potential as immunotherapeutic targets.

Findings

CD8+ T cells exhibit functional heterogeneity in Alzheimer's disease, with both harmful and protective roles.

Transgenic mouse models and clinical data show clonal expansion and antigen experience of CD8+ T cells in AD.

Targeting CD8+ T-cell responses could complement existing immunotherapies for Alzheimer's disease.

Abstract

Amyloid beta plaques and tau tangles are the primary hallmarks of Alzheimer's disease (AD). Recently, passive anti‐Aβ immunotherapy for AD has markedly advanced, as supported by evidence from AD animal models and clinical trials. Whereas innate immunity significantly contributes to AD pathology, it does not fully represent the immune mechanisms linked to this condition. Therefore, focus should be directed toward adaptive immunity, encompassing both humoral and cellular immunity.

Relevant publications and clinical trial data up to February 2026 were systematically reviewed to summarize the mechanisms, therapeutic targets, safety profiles, and translational applications of CD8+ T cells in AD.

Clinical and animal studies have particularly suggested a potential involvement of T cells in AD pathogenesis. T cells that infiltrate the central nervous system (CNS) exert both protective and detrimental effects on neural tissue in AD. Because autoreactive CD8+ T cells are generally expected to have cytotoxic effects on CNS cells, they have received less attention. Nevertheless, accumulating evidence suggests that CD8+ Treg cells are involved in various diseases.

However, the function of anti‐Aβ‐specific CD8+ T cells in Alzheimer's disease (AD) remains ambiguous. Many subsets of CD8+ T cells have been well‐studied in autoimmunity. We suggest that CD8+ T cell subsets identified in AD studies may constitute a promising area for future AD research.

Emerging evidence highlights a previously underappreciated role of CD8+ T cells in Alzheimer's disease (AD). Beyond amyloid‐β and tau pathology, CD8+ T‐cell subsets infiltrate the central nervous system and exhibit functional heterogeneity. Cytotoxic effector CD8+ T cells may exacerbate neuroinflammation and neuronal injury, whereas regulatory or exhausted phenotypes may exert immunomodulatory effects. Findings from transgenic mouse models and clinical immune profiling of peripheral blood and cerebrospinal fluid demonstrate clonal expansion and antigen experience of CD8+ T cells. These translational insights suggest that targeting CD8+ T‐cell responses could represent a complementary immunotherapeutic strategy in AD.

Figures