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Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease
Perrin RJ, Craig-Schapiro R, Malone JP, Shah AR, Gilmore P, Davis AE, Roe CM, Peskind ER et al.. PloS one, 2011-01-12
Topic: Amyloid, tau and blood-test diagnosis
Background Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome. Methods and findings CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR Conclusions Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions.
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APA 7th
Perrin, R. J., Craig-Schapiro, R., Malone, J. P., Shah, A. R., Gilmore, P., Davis, A. E., et al. (2011). Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease. PloS one. https://doi.org/10.1371/journal.pone.0016032
Vancouver
Perrin RJ, Craig-Schapiro R, Malone JP, Shah AR, Gilmore P, Davis AE, et al. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease. PloS one. 2011. doi:10.1371/journal.pone.0016032. PMID: 21264269.
BibTeX
@article{perrin2011-21264269,
author = {Perrin, R. J. and Craig-Schapiro, R. and Malone, J. P. and Shah, A. R. and Gilmore, P. and Davis, A. E. and Roe, C. M. and Peskind, E. R. and others},
title = {{Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease}},
journal = {PloS one},
year = {2011},
doi = {10.1371/journal.pone.0016032},
pmid = {21264269},
url = {https://doi.org/10.1371/journal.pone.0016032}
}
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Key findings
- Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline.
Why it matters
Six cerebrospinal fluid proteins were found to distinguish people with mild Alzheimer's dementia from cognitively normal controls, and these markers were applied to a larger independent group that included very mild dementia. This is a biomarker discovery and validation study and does not show that any treatment, cure, or prevention works.
Study details
- Participants24
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (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 | 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 | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 24 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 174 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.2 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 14.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Anne M. Fagan: h-index 122 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21264269) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
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