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Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles
Tijms BM, Vromen EM, Mjaavatten O, Holstege H, Reus LM, van der Lee S, Wesenhagen KEJ, Lorenzini L et al.. Nature aging, 2024-01-09
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Alzheimer's disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity is critical for AD drug development. Here we define AD molecular subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, with different levels in individuals with AD (n = 419) compared to controls (n = 187).
What this study adds
Evidence grade: Low
The record lists 419 participants. Using mass spectrometry proteomics of cerebrospinal fluid from 419 people with Alzheimer's disease and 187 controls, this study defined five molecular subtypes with distinct genetic risk profiles and different affected processes, such as innate immune activation. It identifies disease heterogeneity relevant to drug development but does not itself report a treatment, cure or prevention.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tijms, B. M., Vromen, E. M., Mjaavatten, O., Holstege, H., Reus, L. M., van der Lee, S., et al. (2024). Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles. Nature aging. https://doi.org/10.1038/s43587-023-00550-7
Vancouver
Tijms BM, Vromen EM, Mjaavatten O, Holstege H, Reus LM, van der Lee S, et al. Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles. Nature aging. 2024. doi:10.1038/s43587-023-00550-7. PMID: 38195725.
BibTeX
@article{tijms2024-38195725,
author = {Tijms, B. M. and Vromen, E. M. and Mjaavatten, O. and Holstege, H. and Reus, L. M. and van der Lee, S. and Wesenhagen, K. E. J. and Lorenzini, L. and others},
title = {{Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles}},
journal = {Nature aging},
year = {2024},
doi = {10.1038/s43587-023-00550-7},
pmid = {38195725},
url = {https://doi.org/10.1038/s43587-023-00550-7}
}
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.
Key findings
- Understanding this heterogeneity is critical for AD drug development.
- Here we define AD molecular subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, with different levels in individuals with AD (n = 419) compared to controls (n = 187).
- These AD subtypes had alterations in protein levels that were associated with distinct molecular processes: subtype 1 was characterized by proteins related to neuronal hyperplasticity; subtype 2 by innate immune activation; subtype 3 by RNA dysregulation; subtype 4 by choroid plexus dysfunction; and subtype 5 by blood-brain barrier impairment.
- Each subtype was related to specific AD genetic risk variants, for example, subtype 1 was enriched with TREM2 R47H.
Why it matters
Using mass spectrometry proteomics of cerebrospinal fluid from 419 people with Alzheimer's disease and 187 controls, this study defined five molecular subtypes with distinct genetic risk profiles and different affected processes, such as innate immune activation. It identifies disease heterogeneity relevant to drug development but does not itself report a treatment, cure or prevention.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Participants419
- Evidence strengthLow
How this study scored 64/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / 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 | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 419 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 204 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 51.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 6 / 6 | Cited 49.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 4 / 4 | Cited 204 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pieter Jelle Visser: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38195725) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
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