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Microglial activation and tau propagate jointly across Braak stages
Pascoal TA, Benedet AL, Ashton NJ, Kang MS, Therriault J, Chamoun M, Savard M, Lussier FZ et al.. Nature medicine, 2021-08-26
Topic: Brain proteins, microglia and lab models
Compelling experimental evidence suggests that microglial activation is involved in the spread of tau tangles over the neocortex in Alzheimer's disease (AD). We tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak-like pattern in the living human brain. We studied 130 individuals across the aging and AD clinical spectrum with positron emission tomography brain imaging for microglial activation ([ 11 C]PBR28), amyloid-β (Aβ) ([ 18 F]AZD4694) and tau ([ 18 F]MK-6240) pathologies.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Pascoal, T. A., Benedet, A. L., Ashton, N. J., Kang, M. S., Therriault, J., Chamoun, M., et al. (2021). Microglial activation and tau propagate jointly across Braak stages. Nature medicine. https://doi.org/10.1038/s41591-021-01456-w
Vancouver
Pascoal TA, Benedet AL, Ashton NJ, Kang MS, Therriault J, Chamoun M, et al. Microglial activation and tau propagate jointly across Braak stages. Nature medicine. 2021. doi:10.1038/s41591-021-01456-w. PMID: 34446931.
BibTeX
@article{pascoal2021-34446931,
author = {Pascoal, T. A. and Benedet, A. L. and Ashton, N. J. and Kang, M. S. and Therriault, J. and Chamoun, M. and Savard, M. and Lussier, F. Z. and others},
title = {{Microglial activation and tau propagate jointly across Braak stages}},
journal = {Nature medicine},
year = {2021},
doi = {10.1038/s41591-021-01456-w},
pmid = {34446931},
url = {https://doi.org/10.1038/s41591-021-01456-w}
}
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Key findings
- We tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak-like pattern in the living human brain.
- We studied 130 individuals across the aging and AD clinical spectrum with positron emission tomography brain imaging for microglial activation ([ 11 C]PBR28), amyloid-β (Aβ) ([ 18 F]AZD4694) and tau ([ 18 F]MK-6240) pathologies.
- We further assessed microglial triggering receptor expressed on myeloid cells 2 (TREM2) cerebrospinal fluid (CSF) concentrations and brain gene expression patterns.
- We found that [ 11 C]PBR28 correlated with CSF soluble TREM2 and showed regional distribution resembling TREM2 gene expression.
Why it matters
In 130 living people, microglial activation and tau accumulation were found to spread together across the brain in a Braak-like pattern. This links microglial activation to tau spread but does not test any treatment.
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Study details
- Study designlongitudinal study
- Participants130
- Evidence strengthModerate
How this study scored 77/100
Published in a top-tier journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 130 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 488 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 69.7 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 6 / 6 | Cited 45.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 35 other studies in this library |
| Still being cited | 4 / 4 | Cited 263 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pedro Rosa‐Neto: h-index 89 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 19 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34446931) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 77 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41591-021-01456-w
- PubMed: 34446931
- Original source →
- Free full text: UCL Discovery (University College London) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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