title: Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease.
abstract: OBJECTIVE
  While plasma biomarkers have been proposed to aid in the clinical diagnosis of Alzheimer disease (AD), few biomarkers have been validated in independent patient cohorts. Here we aim to determine plasma biomarkers associated with AD in 2 independent cohorts and validate the findings in the multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI).
  
  
  METHODS
  Using a targeted proteomic approach, we measured levels of 190 plasma proteins and peptides in 600 participants from 2 independent centers (University of Pennsylvania, Philadelphia; Washington University, St. Louis, MO), and identified 17 analytes associated with the diagnosis of very mild dementia/mild cognitive impairment (MCI) or AD. Four analytes (apoE, B-type natriuretic peptide, C-reactive protein, pancreatic polypeptide) were also found to be altered in clinical MCI/AD in the ADNI cohort (n = 566). Regression analysis showed CSF Aβ42 levels and t-tau/Aβ42 ratios to correlate with the number of APOE4 alleles and plasma levels of B-type natriuretic peptide and pancreatic polypeptide.
  
  
  CONCLUSIONS
  Four plasma analytes were consistently associated with the diagnosis of very mild dementia/MCI/AD in 3 independent clinical cohorts. These plasma biomarkers may predict underlying AD through their association with CSF AD biomarkers, and the association between plasma and CSF amyloid biomarkers needs to be confirmed in a prospective study.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA. william.hu@emory.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Hu
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: Richard
authors.initials: R
authors.lastname: Perrin
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Rebecca
authors.initials: R
authors.lastname: Craig-Schapiro
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clark
authors.forename: Eve
authors.initials: E
authors.lastname: Pickering
authors.forename: Max
authors.initials: M
authors.lastname: Kuhn
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.forename: Leo
authors.initials: L
authors.lastname: McCluskey
authors.forename: Lauren
authors.initials: L
authors.lastname: Elman
authors.forename: Jason
authors.initials: J
authors.lastname: Karlawish
authors.forename: Alice
authors.initials: A
authors.lastname: Chen-Plotkin
authors.forename: Howard I
authors.initials: HI
authors.lastname: Hurtig
authors.forename: Andrew
authors.initials: A
authors.lastname: Siderowf
authors.forename: Frank
authors.initials: F
authors.lastname: Swenson
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Holly
authors.initials: H
authors.lastname: Soares
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D060825:Cognitive Dysfunction / Q000097:blood*; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D009419:Nerve Tissue Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D009419:Nerve Tissue Proteins