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Aβ‐reactive T cell polyfunctionality response as a new biomarker for mild cognitive impairment
Yen‐Ling Chiu, Sui‐Hing Yan, Yang‐Teng Fan, Chiung‐Fang Chang, Ruo‐Wei Hung, Yi‐Chien Liu, TienYu Owen Yang, Yi‐Fang Chuang. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, 2025-01-01
Topic: Brain proteins, microglia and lab models
Abstract Introduction Alzheimer's disease (AD) involves neuroinflammation and amyloid plaque deposition, yet the role of amyloid‐reactive immune response in neurodegeneration remains unclear. We investigate amyloid‐reactive T cell levels in the Epidemiology of Mild Cognitive Impairment Study in Taiwan (EMCIT) and Taiwan Precision Medicine Initiative of Cognitive Impairment and Dementia (TPMIC) cohorts. Method Using diverse amyloid peptide formulations, we established a polyfunctionality assay for five T cell functions and compared mild cognitive impairment (MCI) patients to control subjects in both cohorts. Results In both cohorts, MCI individuals exhibit higher amyloid‐reactive T cell responses than controls. In the TPMIC cohort, CD4+ and CD8+ total response frequencies are notably elevated in MCI (CD4: 1.3%, CD8: 1.91%) versus controls (CD4: 0.15%, CD8: 0.28%; both p < 0.001). Amyloid‐reactive T cell response outperforms plasma phosphorylated tau 181 (p‐tau181) in discriminating MCI (area under the receiver operating characteristic curve CD4+: 0.97; CD8+: 0.96; p‐tau181: 0.72; both p < 0.001). Discussion Amyloid‐reactive T cell polyfunctional response distinguishes MCI from normal aging and could serve as a novel MCI biomarker. Highlights Amyloid‐reactive polyfunctional T cell responses can be detected in the peripheral circulation. Amyloid‐reactive T cell response is significantly enhanced in individuals with mild cognitive impairment compared to age‐matched, cognitively unimpaired individuals. The unique discriminative accuracy of amyloid‐reactive T cell response is significantly higher than phosphorylated tau181 and is not a result of overall T cell hyperreactivity. Future studies are needed to determine the predictive role of amyloid‐reactive T cell responses in disease progression and if the amyloid‐reactive immune response could be a therapeutic target for the treatment of neurodegeneration.
Key findings
- Results In both cohorts, MCI individuals exhibit higher amyloid‐reactive T cell responses than controls.
- In the TPMIC cohort, CD4+ and CD8+ total response frequencies are notably elevated in MCI (CD4: 1.3%, CD8: 1.91%) versus controls (CD4: 0.15%, CD8: 0.28%; both p < 0.001).
- Amyloid‐reactive T cell response is significantly enhanced in individuals with mild cognitive impairment compared to age‐matched, cognitively unimpaired individuals.
- The unique discriminative accuracy of amyloid‐reactive T cell response is significantly higher than phosphorylated tau181 and is not a result of overall T cell hyperreactivity.
Why it matters
This study found that amyloid-reactive T cell responses were higher in people with mild cognitive impairment than in controls and outperformed plasma p-tau181 in discriminating mild cognitive impairment. This could serve as a novel biomarker, but no treatment or cure is tested.
Study details
- Effect size1.3%; 1.91%; 0.15%
- Evidence strengthModerate
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring) |
| Journal's citation record | 1 / 4 | Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring: journal h-index 86 (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 | 3 / 5 | Rated “moderate” 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Yi‐Fang Chuang: h-index 24 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39758054) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/dad2.70042
- PubMed: 39758054
- Original source →
- Free full text: Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Chiu, Y., Yan, S., Fan, Y., Chang, C., Hung, R., Liu, Y., et al. (2025). Aβ‐reactive T cell polyfunctionality response as a new biomarker for mild cognitive impairment. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring. https://doi.org/10.1002/dad2.70042
Vancouver
Chiu Y, Yan S, Fan Y, Chang C, Hung R, Liu Y, et al. Aβ‐reactive T cell polyfunctionality response as a new biomarker for mild cognitive impairment. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring. 2025. doi:10.1002/dad2.70042. PMID: 39758054.
BibTeX
@article{chiu2025-39758054,
author = {Chiu, Yen‐Ling and Yan, Sui‐Hing and Fan, Yang‐Teng and Chang, Chiung‐Fang and Hung, Ruo‐Wei and Liu, Yi‐Chien and Yang, TienYu Owen and Chuang, Yi‐Fang},
title = {{Aβ‐reactive T cell polyfunctionality response as a new biomarker for mild cognitive impairment}},
journal = {Alzheimer s \& Dementia Diagnosis Assessment \& Disease Monitoring},
year = {2025},
doi = {10.1002/dad2.70042},
pmid = {39758054},
url = {https://doi.org/10.1002/dad2.70042}
}
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