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TREM2 gene expression associations with Alzheimer's disease neuropathology are region-specific: implications for cortical versus subcortical microglia
Winfree RL, Seto M, Dumitrescu L, Menon V, De Jager P, Wang Y, Schneider J, Bennett DA et al.. Acta neuropathologica, 2023-03-25
Topic: Brain proteins, microglia and lab models
Previous post-mortem assessments of TREM2 expression and its association with brain pathologies have been limited by sample size. This study sought to correlate region-specific TREM2 mRNA expression with diverse neuropathological measures at autopsy using a large sample size (N = 945) of bulk RNA sequencing data from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP). TREM2 gene expression of the dorsolateral prefrontal cortex, posterior cingulate cortex, and caudate nucleus was assessed with respect to core pathology of Alzheimer's disease (amyloid-β, and tau), cerebrovascular pathology (cerebral infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), microglial activation (proportion of activated microglia), and cognitive performance. We found that cortical TREM2 levels were positively related to AD diagnosis, cognitive decline, and amyloid-β neuropathology but were not related to the proportion of activated microglia. In contrast, caudate TREM2 levels were not related to AD pathology, cognition, or diagnosis, but were positively related to the proportion of activated microglia in the same region. Diagnosis-stratified results revealed caudate TREM2 levels were inversely related to AD neuropathology and positively related to microglial activation and longitudinal cognitive performance in AD cases. These results highlight the notable changes in TREM2 transcript abundance in AD and suggest that its pathological associations are brain-region-dependent.
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APA 7th
Winfree, R. L., Seto, M., Dumitrescu, L., Menon, V., De Jager, P., Wang, Y., et al. (2023). TREM2 gene expression associations with Alzheimer's disease neuropathology are region-specific: implications for cortical versus subcortical microglia. Acta neuropathologica. https://doi.org/10.1007/s00401-023-02564-2
Vancouver
Winfree RL, Seto M, Dumitrescu L, Menon V, De Jager P, Wang Y, et al. TREM2 gene expression associations with Alzheimer's disease neuropathology are region-specific: implications for cortical versus subcortical microglia. Acta neuropathologica. 2023. doi:10.1007/s00401-023-02564-2. PMID: 36966244.
BibTeX
@article{winfree2023-36966244,
author = {Winfree, R. L. and Seto, M. and Dumitrescu, L. and Menon, V. and De Jager, P. and Wang, Y. and Schneider, J. and Bennett, D. A. and others},
title = {{TREM2 gene expression associations with Alzheimer's disease neuropathology are region-specific: implications for cortical versus subcortical microglia}},
journal = {Acta neuropathologica},
year = {2023},
doi = {10.1007/s00401-023-02564-2},
pmid = {36966244},
url = {https://doi.org/10.1007/s00401-023-02564-2}
}
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Key findings
- We found that cortical TREM2 levels were positively related to AD diagnosis, cognitive decline, and amyloid-β neuropathology but were not related to the proportion of activated microglia.
- Diagnosis-stratified results revealed caudate TREM2 levels were inversely related to AD neuropathology and positively related to microglial activation and longitudinal cognitive performance in AD cases.
- These results highlight the notable changes in TREM2 transcript abundance in AD and suggest that its pathological associations are brain-region-dependent.
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Study details
- Study designlongitudinal study
- Participants945
- Evidence strengthModerate
How this study scored 71/100
Published in a leading specialty 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. 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 41 of the 58 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 945 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 | — / 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 36966244) |
| Free to read | 2 / 2 | Free to read |
| Points | 41 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 41 of the 58 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
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