Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers
Jansen IE, van der Lee SJ, Gomez-Fonseca D, de Rojas I, Dalmasso MC, Grenier-Boley B, Zettergren A, Mishra A et al.. Acta neuropathologica, 2022-09-06
Topic: Amyloid, tau and blood-test diagnosis
Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
Key findings
- Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD.
- In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
Why it matters
In the largest combined genetics study of spinal-fluid Alzheimer's markers (31 cohorts, 13,116 people), researchers found that, besides APOE, a variant region near CR1 was linked to amyloid-beta 42 levels, and regions near BIN1, GMNC and C16orf95 were linked to phosphorylated tau; C16orf95 had not been reported before. Grouping all known Alzheimer's risk genes by their effect on these markers gave four clusters, suggesting several separate biological routes into the disease. GMNC and C16orf95 were also linked to the size of the brain's fluid-filled ventricles, hinting that tau levels and brain structure share some genetic roots. These are associations, not a test or a treatment.
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Study details
- Participants8,074
- Evidence strengthLow
How this study scored 73/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported 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 | 12 / 12 | A meta-analysis pooling many studies (from PubMed type “Meta-Analysis”) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 3 / 4 | 8,074 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 | A review of other studies — randomisation is not credited here |
| Times cited | 5 / 7 | Cited 135 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.5 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 4 / 6 | Cited 14.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 106 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Inez Ramakers: h-index 7 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 98 institution(s) in 14 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36066633) |
| Free to read | 2 / 2 | Free to read |
| Total | 73 / 100 | — |
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Read the original
- DOI: 10.1007/s00401-022-02454-z
- PubMed: 36066633
- 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
Jansen, I. E., van der Lee, S. J., Gomez-Fonseca, D., de Rojas, I., Dalmasso, M. C., Grenier-Boley, B., et al. (2022). Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. Acta neuropathologica. https://doi.org/10.1007/s00401-022-02454-z
Vancouver
Jansen IE, van der Lee SJ, Gomez-Fonseca D, de Rojas I, Dalmasso MC, Grenier-Boley B, et al. Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. Acta neuropathologica. 2022. doi:10.1007/s00401-022-02454-z. PMID: 36066633.
BibTeX
@article{jansen2022-36066633,
author = {Jansen, I. E. and van der Lee, S. J. and Gomez-Fonseca, D. and de Rojas, I. and Dalmasso, M. C. and Grenier-Boley, B. and Zettergren, A. and Mishra, A. and others},
title = {{Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers}},
journal = {Acta neuropathologica},
year = {2022},
doi = {10.1007/s00401-022-02454-z},
pmid = {36066633},
url = {https://doi.org/10.1007/s00401-022-02454-z}
}
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