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Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF
Spellman DS, Wildsmith KR, Honigberg LA, Tuefferd M, Baker D, Raghavan N, Nairn AC, Croteau P et al.. Proteomics. Clinical applications, 2015-04-24
Topic: Amyloid, tau and blood-test diagnosis
Purpose We describe the outcome of the Biomarkers Consortium CSF Proteomics Project (where CSF is cerebral spinal fluid), a public-private partnership of government, academia, nonprofit, and industry. The goal of this study was to evaluate a multiplexed MS-based approach for the qualification of candidate Alzheimer's disease (AD) biomarkers using CSF samples from the AD Neuroimaging Initiative. Experimental design Reproducibility of sample processing, analytic variability, and ability to detect a variety of analytes of interest were thoroughly investigated. Multiple approaches to statistical analyses assessed whether panel analytes were associated with baseline pathology (mild cognitive impairment (MCI), AD) versus healthy controls or associated with progression for MCI patients, and included (i) univariate association analyses, (ii) univariate prediction models, (iii) exploratory multivariate analyses, and (iv) supervised multivariate analysis. Results A robust targeted MS-based approach for the qualification of candidate AD biomarkers was developed. The results identified several peptides with potential diagnostic or predictive utility, with the most significant differences observed for the following peptides for differentiating (including peptides from hemoglobin A, hemoglobin B, and superoxide dismutase) or predicting (including peptides from neuronal pentraxin-2, neurosecretory protein VGF (VGF), and secretogranin-2) progression versus nonprogression from MCI to AD. Conclusions and clinical relevance These data provide potential insights into the biology of CSF in AD and MCI progression and provide a novel tool for AD researchers and clinicians working to improve diagnostic accuracy, evaluation of treatment efficacy, and early diagnosis.
Key findings
- Multiple approaches to statistical analyses assessed whether panel analytes were associated with baseline pathology (mild cognitive impairment (MCI), AD) versus healthy controls or associated with progression for MCI patients, and included (i) univariate association analyses, (ii) univariate prediction models, (iii) exploratory multivariate analyses, and (iv) supervised multivariate analysis.
- Results A robust targeted MS-based approach for the qualification of candidate AD biomarkers was developed.
- The results identified several peptides with potential diagnostic or predictive utility, with the most significant differences observed for the following peptides for differentiating (including peptides from hemoglobin A, hemoglobin B, and superoxide dismutase) or predicting (including peptides from neuronal pentraxin-2, neurosecretory protein VGF (VGF), and secretogranin-2) progression versus nonprogression from MCI to AD.
Why it matters
This project developed a multiplexed mass spectrometry-based approach for measuring candidate Alzheimer's disease biomarkers in cerebrospinal fluid, identifying several peptides with potential diagnostic or predictive utility. The work concerns biomarker measurement and qualification, not treating, curing, or preventing the disease.
Study details
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 40 of the 96 points we could judge it on, which is 42 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proteomics. Clinical applications) |
| Journal's citation record | 0 / 4 | PROTEOMICS - CLINICAL APPLICATIONS: journal h-index 74 (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 | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 159 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.2 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 3 / 6 | Cited 6.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 44 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25676562) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 40 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 40 of the 96 points we could judge it on is 42 out of 100. |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Spellman, D. S., Wildsmith, K. R., Honigberg, L. A., Tuefferd, M., Baker, D., Raghavan, N., et al. (2015). Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF. Proteomics. Clinical applications. https://doi.org/10.1002/prca.201400178
Vancouver
Spellman DS, Wildsmith KR, Honigberg LA, Tuefferd M, Baker D, Raghavan N, et al. Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF. Proteomics. Clinical applications. 2015. doi:10.1002/prca.201400178. PMID: 25676562.
BibTeX
@article{spellman2015-25676562,
author = {Spellman, D. S. and Wildsmith, K. R. and Honigberg, L. A. and Tuefferd, M. and Baker, D. and Raghavan, N. and Nairn, A. C. and Croteau, P. and others},
title = {{Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF}},
journal = {Proteomics. Clinical applications},
year = {2015},
doi = {10.1002/prca.201400178},
pmid = {25676562},
url = {https://doi.org/10.1002/prca.201400178}
}
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