title: A candidate plasma protein classifier to identify Alzheimer's disease.
abstract: Biomarkers currently used in the aid for the diagnosis of Alzheimer's disease (AD) are cerebrospinal fluid (CSF) protein markers and brain neuroimaging markers. These biomarkers, however, either involve semi-invasive procedures or are costly to measure. Thus, AD biomarkers from more easily accessible body fluids, such as plasma, are very enticing. Using an aptamer-based proteomic technology, we profiled 1,129 plasma proteins of AD patients and non-demented control individuals. A 5-protein classifier for AD identification was constructed in the discovery study with excellent 10-fold cross-validation performance (90.1% sensitivity, 84.2% specificity, 87.9% accuracy, and AUC as 0.94). In an independent validation study, the classifier was applied and correctly predicted AD with 100.0% sensitivity, 80.0% specificity, and 90.0% accuracy, matching or outperforming the CSF Aβ42 and tau biomarkers whose performance were assessed in individual-matched CSF samples obtained at the same visit as plasma sample collection. Moreover, the classifier also correctly predicted mild cognitive impairment, an early pre-dementia state of the disease, with 96.7% sensitivity, 80.0% specificity, and 92.5% accuracy. These studies demonstrate that plasma proteins could be used effectively and accurately to contribute to the clinical diagnosis of AD. Although additional and more diverse cohorts are needed for further validation of the robustness, including the support of postmortem diagnosis, the 5-protein classifier appears to be a promising blood test to contribute diagnosis of AD.
authors.affiliation: Molecular Biomarkers and Diagnostics Laboratory, Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Informatics and Analysis, Merck Research Laboratories, Boston, MA, USA.
authors.forename: Serguei
authors.initials: S
authors.lastname: Lejnine
authors.affiliation: Molecular Biomarkers and Diagnostics Laboratory, Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Spond
authors.affiliation: Informatics and Analysis, Merck Research Laboratories, Boston, MA, USA.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Biometrics Research, Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Ramaraj
authors.affiliation: Biometrics Research, Merck Research Laboratories, West Point, PA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Holder
authors.affiliation: Informatics and Analysis, Merck Research Laboratories, Boston, MA, USA.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.affiliation: Molecular Biomarkers and Diagnostics Laboratory, Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Weiner
authors.affiliation: Molecular Biomarkers and Diagnostics Laboratory, Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Omar F
authors.initials: OF
authors.lastname: Laterza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D019540:Area Under Curve; D001798:Blood Proteins / Q000145:classification* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D040901:Proteomics; D015203:Reproducibility of Results; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001798:Blood Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; aptamers; biomarkers; blood; proteome