Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF
Open accessAbstract
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.
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A mass spectrometry-based approach revealed NPTX2 as one of the best markers to differentiate between progressive and non-progressive MCI.
“A mass spectrometry-based approach revealed NPTX2 as one of the best markers to differentiate between progressive and non-progressive MCI (Spellman et al. 2015).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Spellman et al. 2015
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- Authors
- Spellman, D. S., Wildsmith, K. R., Honigberg, L. A., Tuefferd, M., Baker, D., Raghavan, N., Nairn, A. C., Croteau, P., Schirm, M., Allard, R., Lamontagne, J., Chelsky, D., Hoffmann, S., Potter, W. Z., & Initiative, A. D. N.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Roche (United States) (US)
- Janssen (Belgium) (BE)
- Janssen Research & Development LLC Titusville NJ USA
- Yale University (US)
- Caprion (Canada) (CA)
- Caprion Pharmaceuticals Montreal QC Canada
- Foundation for the National Institutes of Health (US)
- National Institute of Mental Health (US)
- Alzheimer’s Disease Neuroimaging Initiative (US)
- Corresponding author
- Spellman, Daniel S.
- ORCID
- Venue
- PROTEOMICS – Clinical Applications
- Publisher
- Wiley
- Published
- 2015-04-24
- Volume
- 9
- Issue
- 7-8
- Pages
- 715-731
- ISSN
- 1862-8346 (ISSN-L)
- 1862-8354
- PMC
- PMC4739636
- OpenAlex
- W1968352263
- Cited by
- 161
- References
- 60
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 17 · 2023: 11 · 2022: 15 · 2021: 13 · 2020: 32 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 9 · 2015: 3
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- PROTEOMICS - CLINICAL APPLICATIONS (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904, P50AG047270)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- Alzheimer's disease, cerebrospinal fluid, peptide biomarkers, targeted mass spectrometry, multiplex assay, mild cognitive impairment, neuroimaging biomarkers, superoxide dismutase, VGF, diagnostic biomarkers, early diagnosis
- MeSH terms
- Aged, Alzheimer Disease, Amino Acid Sequence, Apolipoproteins E, Biological Assay, Female, Humans, Male, Molecular Sequence Data, Peptides, Quality Control, Mass Spectrometry, Statistics as Topic, Reproducibility of Results, Biomarkers, Disease Progression, Area Under Curve, Principal Component Analysis, Neuroimaging, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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