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PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment
Kleineidam L, Chouraki V, Próchnicki T, van der Lee SJ, Madrid-Márquez L, Wagner-Thelen H, Karaca I, Weinhold L et al.. Acta neuropathologica, 2020-03-12
Topic: Brain proteins, microglia and lab models
A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer's disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau 181 , total tau, and Aβ 1-42 was assessed in 1261 MCI patients.
Key findings
- To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies.
- Furthermore, association with CSF levels of pTau 181 , total tau, and Aβ 1-42 was assessed in 1261 MCI patients.
- We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau 181 levels in CSF.
- The effect size of the association of p.P522R with the cognitive decline and pTau 181 was similar to that of APOE-ε4, the strongest genetic risk factor for AD.
Why it matters
In 3595 patients with mild cognitive impairment, carriers of the PLCG2 p.P522R variant showed a slower rate of cognitive decline than non-carriers. This is an observational genetic study and reports no treatment, cure or prevention.
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Study details
- Study designlongitudinal study
- Participants10,097
- Evidence strengthModerate
How this study scored 67/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 4 / 4 | 10,097 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 | 4 / 7 | Cited 65 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.1 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 24 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alfredo Ramı́rez: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 47 institution(s) in 9 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32166339) |
| Free to read | 2 / 2 | Free to read |
| Total | 67 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s00401-020-02138-6
- PubMed: 32166339
- Original source →
- Free full text: Acta Neuropathologica →
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
Kleineidam, L., Chouraki, V., Próchnicki, T., van der Lee, S. J., Madrid-Márquez, L., Wagner-Thelen, H., et al. (2020). PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment. Acta neuropathologica. https://doi.org/10.1007/s00401-020-02138-6
Vancouver
Kleineidam L, Chouraki V, Próchnicki T, van der Lee SJ, Madrid-Márquez L, Wagner-Thelen H, et al. PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment. Acta neuropathologica. 2020. doi:10.1007/s00401-020-02138-6. PMID: 32166339.
BibTeX
@article{kleineidam2020-32166339,
author = {Kleineidam, L. and Chouraki, V. and Próchnicki, T. and van der Lee, S. J. and Madrid-Márquez, L. and Wagner-Thelen, H. and Karaca, I. and Weinhold, L. and others},
title = {{PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment}},
journal = {Acta neuropathologica},
year = {2020},
doi = {10.1007/s00401-020-02138-6},
pmid = {32166339},
url = {https://doi.org/10.1007/s00401-020-02138-6}
}
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