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Multi-tissue proteomics identifies molecular signatures for sporadic and genetically defined Alzheimer disease cases
Cruchaga C, Sung YJ, Yang C, Wang F, Suhy A, Norton J, Novotny B, Etelleb A et al.. Research Square, 2021-10-21
Topic: Amyloid, tau and blood-test diagnosis
Abstract Alzheimer disease (AD) is a heterogeneous disease with many genes are associated with AD risk. Most proteomic studies, while instrumental in identifying AD pathways and genes, focus on single tissues and sporadic AD cases. Multi-tissue proteomic signatures for sporadic and genetically defined AD (e.g., pathogenic variant carriers in APP and PSEN1/2 and risk variant carriers in TREM2) will illuminate the biology of this heterogeneous disease.1,2 Here, we present one of the largest multi-tissue proteomic profiles, accessible through our web portal, based on 1,305 proteins in brain (n=360), cerebrospinal fluid (CSF; n=717), and plasma (n=490) from the Knight Alzheimer Disease Research Center (Knight ADRC) and Dominantly Inherited Alzheimer Network (DIAN) cohorts.3-5 We identified proteomic signatures in brain, CSF, and plasma for sporadic AD status and replicated these findings in
Key findings
- Most proteomic studies, while instrumental in identifying AD pathways and genes, focus on single tissues and sporadic AD cases.
- Multi-tissue proteomic signatures for sporadic and genetically defined AD (e.g., pathogenic variant carriers in APP and PSEN1/2 and risk variant carriers in TREM2) will illuminate the biology of this heterogeneous disease.1,2 Here, we present one of the largest multi-tissue proteomic profiles, accessible through our web portal, based on 1,305 proteins in brain (n=360), cerebrospinal fluid (CSF; n=717), and plasma (n=490) from the Knight Alzheimer Disease Research Center (Knight ADRC) and Dominantly Inherited Alzheimer Network (DIAN) cohorts.3-5 We identified proteomic signatures in brain, CSF, and plasma for sporadic AD status and replicated these findings in multiple, independent datasets.
- The area under the curve (AUC) for CSF proteins was 0.89 in discovery and 0.90 in the replication dataset, which was significantly higher than the AUC for CSF p-tau181/Aβ42 (AUC = 0.81; P = 2.4×10-6).
- We also identified a specific proteomic signature for TREM2 variant carriers that differentiated TREM2 variant carriers from sporadic AD cases and controls with high sensitivity and specificity (AUC = 0.81 - 1).
Why it matters
This work compared proteins in brain, cerebrospinal fluid, and plasma from people with sporadic and genetically defined Alzheimer's disease, and found a cerebrospinal fluid protein signature that distinguished cases with an area under the curve of 0.89 in the discovery group. It is a biomarker study, so it may help identify disease signatures but does not by itself show a way to treat, cure, or prevent Alzheimer's disease.
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Study details
- Participants360
- Effect sizeAUC = 0.81
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 30 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 28 of the 94 points we could judge it on, which is 30 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 360 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.6 citations a year over 7 year(s) since 2021 |
| 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 | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Oscar Harari: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 28 of the 94 points we could judge it on is 30 out of 100. |
| Total | 30 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Cruchaga, C., Sung, Y. J., Yang, C., Wang, F., Suhy, A., Norton, J., et al. (2021). Multi-tissue proteomics identifies molecular signatures for sporadic and genetically defined Alzheimer disease cases. Research Square. https://doi.org/10.21203/rs.3.rs-923492/v1
Vancouver
Cruchaga C, Sung YJ, Yang C, Wang F, Suhy A, Norton J, et al. Multi-tissue proteomics identifies molecular signatures for sporadic and genetically defined Alzheimer disease cases. Research Square. 2021. doi:10.21203/rs.3.rs-923492/v1.
BibTeX
@article{cruchaga2021-91194d89,
author = {Cruchaga, C. and Sung, Y. J. and Yang, C. and Wang, F. and Suhy, A. and Norton, J. and Novotny, B. and Etelleb, A. and others},
title = {{Multi-tissue proteomics identifies molecular signatures for sporadic and genetically defined Alzheimer disease cases}},
journal = {Research Square},
year = {2021},
doi = {10.21203/rs.3.rs-923492/v1},
url = {https://doi.org/10.21203/rs.3.rs-923492/v1}
}
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