title: Plasma protein profiling of mild cognitive impairment and Alzheimer's disease across two independent cohorts.
abstract: To unlock the full potential of disease modifying treatments, it is essential to develop early biomarkers for Alzheimer's disease (AD). For practical reasons, blood-based markers that could provide a signal at the stage of mild cognitive impairment (MCI) or even earlier would be ideal. Using the proteomic approach of isobaric tagging for relative and absolute quantitation (iTRAQ), we compared the plasma protein profiles of MCI, AD, and cognitively normal control subjects from two independent cohorts: the Sydney Memory and Ageing Study (261 MCI subjects, 24 AD subjects, 411 controls) and the Hunter Community Study (180 MCI subjects, 153 controls). The objective was to identify any proteins that are differentially abundant in MCI and AD plasma in both cohorts, since they might be of interest as potential biomarkers, or could help direct future mechanistic studies. Proteins representative of biological processes relevant to AD pathology, such as the complement system, the coagulation cascade, lipid metabolism, and metal and vitamin D and E transport, were found to differ in abundance in MCI. In particular, levels of complement regulators C1 inhibitor and factor H, fibronectin, ceruloplasmin, and vitamin D-binding protein were significantly decreased in MCI participants from both cohorts. Several apolipoproteins, including apolipoprotein AIV, B-100, and H were also significantly decreased in MCI. Most of these proteins have previously been reported as potential biomarkers for AD; however, we show for the first time that a significant decrease in plasma levels of two potential biomarkers (fibronectin and C1 inhibitor) is evident at the MCI stage.
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Muenchhoff
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.affiliation: Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Raftery
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Denver-School of Medicine, Aurora, Colorado, USA Biodesix Inc., Boulder, Colorado, USA Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mark
authors.initials: M
authors.lastname: Duncan
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: McEvoy
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, Australia School of Psychology, University of Newcastle, Newcastle, Australia.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schofield
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D060825:Cognitive Dysfunction / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; apolipoproteins; biomarkers; complement system proteins; fibrinogen; fibronectin; mild cognitive impairment; plasma; proteomics; vitamin D-binding protein