T cell drives microglia specific metabolic plasticity and neurodegeneration in Alzheimer disease 4098
Xiaoying Chen. The Journal of Immunology, 2025-11-01
Topic: Amyloid, tau and blood-test diagnosis
Abstract Description The regional progression of brain atrophy in Alzheimer’s disease highly correlates with tau accumulation. There are changes in adaptive immunity in AD and the increases in activated CD8+ T cells in the brain correlate with tau pathology. Further, there is a dynamic transformation of the CD8+ T cell cellular characteristics from activated to exhausted states along with unique TCR clonal expansion. Depletion of brain-resident microglia, infiltrated T cells, as well as, inhibiting IFN-γ signaling all significantly ameliorated brain atrophy. To date, little is known about the interaction between T cells and brain resident microglia. Here we use APOE isoforms-dependent mouse models and human neuroimmune axis models to show that microglia coordinate immune modulatory response against immune challenges in AD. Adaptive immune deficiency had strongly decreased microglial reactivity and microglia-mediated synaptic engulfment in tauopathy. Adaptive Immune deficiency ameliorates Tau-linked glial lipid accumulation. Of note, using large-scale transcriptome and chromatin profiling, we show that T cell shape microglia-specific metabolic plasticity in both genetic and epigenetic resolution. Our results thus reveal a tauopathy and neurodegeneration-related immune hub involving activated microglia and T cell responses, which could potentially serve as therapeutic targets for preventing neurodegeneration in AD and primary tauopathies. Funding Sources This research was supported by Cure Alzheimer’s Foundation and Alzheimer’s Association Foundation. Topic Categories Neuroimmunology (NEUR)
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Chen, X. (2025). T cell drives microglia specific metabolic plasticity and neurodegeneration in Alzheimer disease 4098. The Journal of Immunology. https://doi.org/10.1093/jimmun/vkaf283.1823
Vancouver
Chen X. T cell drives microglia specific metabolic plasticity and neurodegeneration in Alzheimer disease 4098. The Journal of Immunology. 2025. doi:10.1093/jimmun/vkaf283.1823.
BibTeX
@article{chen2025-1d3c79ca,
author = {Chen, Xiaoying},
title = {{T cell drives microglia specific metabolic plasticity and neurodegeneration in Alzheimer disease 4098}},
journal = {The Journal of Immunology},
year = {2025},
doi = {10.1093/jimmun/vkaf283.1823},
url = {https://doi.org/10.1093/jimmun/vkaf283.1823}
}
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Key findings
- Depletion of brain-resident microglia, infiltrated T cells, as well as, inhibiting IFN-γ signaling all significantly ameliorated brain atrophy.
- Our results thus reveal a tauopathy and neurodegeneration-related immune hub involving activated microglia and T cell responses, which could potentially serve as therapeutic targets for preventing neurodegeneration in AD and primary tauopathies.
Why it matters
Depletion of microglia, infiltrated T cells, or inhibition of IFN-γ signaling ameliorated brain atrophy in mouse models, revealing an immune hub involving activated microglia and T cell responses. These findings suggest potential therapeutic targets for preventing neurodegeneration in Alzheimer's disease and primary tauopathies.
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Study details
- Evidence strengthLow
How this study scored 31/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record and institution's track record, so those were left out: it earned 29 of the 93 points we could judge it on, which is 31 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Immunology) |
| Journal's citation record | 4 / 4 | The Journal of Immunology: journal h-index 531 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 29 / 93 | Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 29 of the 93 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | — |
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