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Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease
Gate D, Saligrama N, Leventhal O, Yang AC, Unger MS, Middeldorp J, Chen K, Lehallier B et al.. Nature, 2020-01-08
Topic: Inflammation, microglia and astrocytes
Alzheimer's disease is an incurable neurodegenerative disorder in which neuroinflammation has a critical function 1 . However, little is known about the contribution of the adaptive immune response in Alzheimer's disease 2 . Here, using integrated analyses of multiple cohorts, we identify peripheral and central adaptive immune changes in Alzheimer's disease. First, we performed mass cytometry of peripheral blood mononuclear cells and discovered an immune signature of Alzheimer's disease that consists of increased numbers of CD8 + T effector memory CD45RA + (T EMRA ) cells. In a second cohort, we found that CD8 + T EMRA cells were negatively associated with cognition. Furthermore, single-cell RNA sequencing revealed that T cell receptor (TCR) signalling was enhanced in these cells. Notably, by using several strategies of single-cell TCR sequencing in a third cohort, we discovered clonally expanded CD8 + T EMRA cells in the cerebrospinal fluid of patients with Alzheimer's disease. Finally, we used machine learning, cloning and peptide screens to demonstrate the specificity of clonally expanded TCRs in the cerebrospinal fluid of patients with Alzheimer's disease to two separate Epstein-Barr virus antigens. These results reveal an adaptive immune response in the blood and cerebrospinal fluid in Alzheimer's disease and provide evidence of clonal, antigen-experienced T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration.
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APA 7th
Gate, D., Saligrama, N., Leventhal, O., Yang, A. C., Unger, M. S., Middeldorp, J., et al. (2020). Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease. Nature. https://doi.org/10.1038/s41586-019-1895-7
Vancouver
Gate D, Saligrama N, Leventhal O, Yang AC, Unger MS, Middeldorp J, et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease. Nature. 2020. doi:10.1038/s41586-019-1895-7. PMID: 31915375.
BibTeX
@article{gate2020-31915375,
author = {Gate, D. and Saligrama, N. and Leventhal, O. and Yang, A. C. and Unger, M. S. and Middeldorp, J. and Chen, K. and Lehallier, B. and others},
title = {{Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease}},
journal = {Nature},
year = {2020},
doi = {10.1038/s41586-019-1895-7},
pmid = {31915375},
url = {https://doi.org/10.1038/s41586-019-1895-7}
}
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Key findings
- In a second cohort, we found that CD8 + T EMRA cells were negatively associated with cognition.
- Furthermore, single-cell RNA sequencing revealed that T cell receptor (TCR) signalling was enhanced in these cells.
- These results reveal an adaptive immune response in the blood and cerebrospinal fluid in Alzheimer's disease and provide evidence of clonal, antigen-experienced T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration.
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Study details
- Evidence strengthModerate
How this study scored 47/100
Published in a top-tier 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 journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2 / 5 | 2020 — within 10 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| 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 | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31915375) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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