ArticleBrain : a journal of neurology2025
Altered T-cell reactivity in the early stages of Alzheimer's disease.
Article in Brain : a journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Immunotherapy with a short-lived anti-PD-L1 antibody in Alzheimer's disease: a phase 1b, randomized, double-blind trial.Nature medicine · 2026Trial
- Hospital-treated infection associated with Alzheimer's disease pathology: underlying mechanisms.Molecular psychiatry · 2026Review
- ZBP1-mediated Treg cell dysfunction exacerbates neuroimmune dysregulation in Alzheimer's disease under metabolic stress.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Emerging roles of granzymes in neurodegeneration and neuroinflammation: mechanistic insights and therapeutic opportunities.Acta neuropathologica · 2026Review
- The Neuroimmune Duality of CD4⁺ T Cells: Drivers of Damage and Repair in the Brain.Molecular neurobiology · 2026Review
- Human brain connectome profiles mediate the relationship between pathology burden and clinical phenotypes in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Adaptive immunity in the pathogenesis of neurodegeneration.Nature immunology · 2026Review
- Challenge-based ex vivo immune profiling reveals stimulus-dependent peripheral immune reprogramming in Alzheimer's disease.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Lymphoid-like Suppressive Microglia in Alzheimer's Disease: A New Neuroimmune Regulatory Axis?Cells · 2026Review
- Reprogramming Neuroinflammation: Mitochondrial Targets and Immune Checkpoint Inhibitors in Alzheimer's Disease.Molecular neurobiology · 2026Review
- The Immune-Chemokine Axis in Alzheimer's Disease: Roles of Adaptive Immune System in Neuroinflammation and Disease Progression.Biomolecules · 2026Review
- The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Single-cell analysis of the peripheral immune landscape in Parkinson's disease: insights into dendritic cell and CD4+ T-cell transcriptomics.NPJ Parkinson's disease · 2026Article
- HMGB1 dysregulation: a neuroimmune bridge to cognitive impairment in autoimmune thyroiditis.Frontiers in immunology · 2026Article
- Association between Alzheimer's disease and MHC-I antigen processing and presentation pathway: a narrative review.Frontiers in immunology · 2026Review
- Adaptive Immunity and Alzheimer's Disease: Dual Roles in Neurodegeneration and Neuroprotection with Therapeutic Implications.Biomolecules & therapeutics · 2026Review
- Spilling the T: T cells in tauopathy mechanisms, disease progression, and therapeutic horizons.Molecular neurodegeneration advances · 2026Review
- Review
- Cerebrospinal fluid protein elevations in Alzheimer's disease are dissociated from immune cell composition.Alzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The adaptive immune system and neurodegenerative Alzheimer's disease (AD) are intertwined in multiple ways. Recent studies have reported alterations of the adaptive immune system in early AD stages, such as preclinical AD and mild cognitive impairment (MCI) due to AD. However, the identity of specific antigenic targets and whether the respective response is beneficial or detrimental during disease progression are still open questions. Herein, we describe cross-sectional analyses of blood and CSF from three different study populations covering early AD stages. We employed high-dimensional mass cytometry, single-cell RNA-sequencing, ex vivo T-cell secretome analysis, and antigen presentation assays to achieve a comprehensive characterization of adaptive immune cell populations. Our results show that subjects at the stage of asymptomatic, preclinical AD can mount a CD4+ T helper cell response towards amyloid-β peptide and display an early enrichment of CD8+ T effector memory cells re-expressing CD45RA (TEMRA cells) in CSF, combined with a less immunosuppressive gene signature of peripheral regulatory T cells. Conversely, in MCI we observed increased frequencies of CD8+ TEMRA/effector cells in the periphery characterized by a pro-inflammatory gene expression profile, and generally decreased antigen responsiveness. Our results demonstrate the complexity of adaptive immune changes in early AD and suggest that it may be beneficial to promote specific CD4+ T-cell responses in the preclinical stage, while in MCI it may be important to therapeutically target CD8+ T-cell responses if these prove to be harmful.
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Registered trials
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