title: Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  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.
authors: Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Pennsylvania, PA, USA.
authors: Daniel S
authors: DS
authors: Spellman
authors: Department of Pharmacodynamic Biomarkers within Development Sciences, Genentech, Inc (a member of the Roche Group), South San Francisco, CA, USA.
authors: Kristin R
authors: KR
authors: Wildsmith
authors: Department of Pharmacodynamic Biomarkers within Development Sciences, Genentech, Inc (a member of the Roche Group), South San Francisco, CA, USA.
authors: Lee A
authors: LA
authors: Honigberg
authors: Discovery Sciences, Janssen Research & Development LLC, Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium.
authors: Marianne
authors: M
authors: Tuefferd
authors: Janssen Research & Development LLC, Titusville, NJ, USA.
authors: David
authors: D
authors: Baker
authors: Janssen Research & Development LLC, Titusville, NJ, USA.
authors: Nandini
authors: N
authors: Raghavan
authors: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Angus C
authors: AC
authors: Nairn
authors: Caprion Pharmaceuticals, Montreal, QC, Canada.
authors: Pascal
authors: P
authors: Croteau
authors: Caprion Pharmaceuticals, Montreal, QC, Canada.
authors: Michael
authors: M
authors: Schirm
authors: Caprion Pharmaceuticals, Montreal, QC, Canada.
authors: Rene
authors: R
authors: Allard
authors: Caprion Pharmaceuticals, Montreal, QC, Canada.
authors: Julie
authors: J
authors: Lamontagne
authors: Caprion Pharmaceuticals, Montreal, QC, Canada.
authors: Daniel
authors: D
authors: Chelsky
authors: Foundation for the National Institutes of Health, Inc, Bethesda, MD, USA.
authors: Steven
authors: S
authors: Hoffmann
authors: National Institute of Mental Health, Bethesda, MD, USA.
authors: William Z
authors: WZ
authors: Potter
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology; D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid; D019540:Area Under Curve; D001681:Biological Assay / Q000379:methods*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D059906:Neuroimaging / Q000379:methods*; D010455:Peptides / Q000134:cerebrospinal fluid / Q000737:chemistry; D025341:Principal Component Analysis; D011786:Quality Control; D015203:Reproducibility of Results; D013223:Statistics as Topic
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D010455:Peptides
keywords: Alzheimer's disease; Biomarkers; Mass spectrometry; Targeted proteomics