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Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer's disease pathology
Pereira JB, Janelidze S, Strandberg O, Whelan CD, Zetterberg H, Blennow K, Palmqvist S, Stomrud E et al.. Nature aging, 2022-11-28
Topic: Brain proteins, microglia and lab models
The role of microglia in tau accumulation is currently unclear but could provide an important insight into the mechanisms underlying Alzheimer's disease (AD) 1 . Here, we measured the microglial marker soluble TREM2 and the disease-associated microglial activation stage 2 markers AXL, MERTK, GAS6, LPL, CST7, SPP1 and CSF1 in nondemented individuals from the Swedish BioFINDER-2 cohort who underwent longitudinal tau-positron emission tomography (PET), amyloid-PET and global cognitive assessment. To assess whether baseline microglial markers had an effect on AD-related changes, we studied three sub-groups of individuals: 121 with evidence of amyloid-PET pathology (A + ), 64 with additional evidence of tau-PET pathology (A + T + ) and 159 without amyloid- or tau-PET pathology (A - T - ).
Key findings
- Here, we measured the microglial marker soluble TREM2 and the disease-associated microglial activation stage 2 markers AXL, MERTK, GAS6, LPL, CST7, SPP1 and CSF1 in nondemented individuals from the Swedish BioFINDER-2 cohort who underwent longitudinal tau-positron emission tomography (PET), amyloid-PET and global cognitive assessment.
- To assess whether baseline microglial markers had an effect on AD-related changes, we studied three sub-groups of individuals: 121 with evidence of amyloid-PET pathology (A + ), 64 with additional evidence of tau-PET pathology (A + T + ) and 159 without amyloid- or tau-PET pathology (A - T - ).
- Our results showed that increased levels of TREM2 were associated with slower amyloid accumulation in A + individuals in addition to slower tau deposition and cognitive decline in A + T + subjects.
- Similarly, higher levels of AXL, MERTK, GAS6, LPL, CST7 and CSF1 predicted slower tau accumulation and/or cognitive decline in the A + T + group.
Why it matters
In a Swedish cohort of people without dementia, those with Alzheimer's-type amyloid on PET (121) who had higher soluble TREM2, a microglial marker, showed slower amyloid build-up. In those who also had tau on PET (64), higher TREM2 and several related microglial markers went with slower tau accumulation and/or slower cognitive decline. These are associations from observational data. No treatment was tested, and the study does not show that boosting microglia slows Alzheimer's.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 60/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (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 | 2022 — within 6 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 | 4 / 7 | Cited 83 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.8 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 5.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 3 / 4 | Cited 70 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Oskar Hansson: h-index 148 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37118533) |
| Free to read | 2 / 2 | Free to read |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Pereira, J. B., Janelidze, S., Strandberg, O., Whelan, C. D., Zetterberg, H., Blennow, K., et al. (2022). Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer's disease pathology. Nature aging. https://doi.org/10.1038/s43587-022-00310-z
Vancouver
Pereira JB, Janelidze S, Strandberg O, Whelan CD, Zetterberg H, Blennow K, et al. Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer's disease pathology. Nature aging. 2022. doi:10.1038/s43587-022-00310-z. PMID: 37118533.
BibTeX
@article{pereira2022-37118533,
author = {Pereira, J. B. and Janelidze, S. and Strandberg, O. and Whelan, C. D. and Zetterberg, H. and Blennow, K. and Palmqvist, S. and Stomrud, E. and others},
title = {{Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer's disease pathology}},
journal = {Nature aging},
year = {2022},
doi = {10.1038/s43587-022-00310-z},
pmid = {37118533},
url = {https://doi.org/10.1038/s43587-022-00310-z}
}
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