title: A platelet protein biochip rapidly detects an Alzheimer's disease-specific phenotype.
abstract: Alzheimer's disease (AD), a multifactorial neurodegenerative condition caused by genetic and environmental factors, is diagnosed using neuropsychological tests and brain imaging; molecular diagnostics are not routinely applied. Studies have identified AD-specific cerebrospinal fluid (CSF) biomarkers but sample collection requires invasive lumbar puncture. To identify AD-modulated proteins in easily accessible blood platelets, which share biochemical signatures with neurons, we compared platelet lysates from 62 AD, 24 amnestic mild cognitive impairment (aMCI), 13 vascular dementia (VaD), and 12 Parkinson's disease (PD) patients with those of 112 matched controls by fluorescence two-dimensional differential gel electrophoresis in independent discovery and verification sets. The optimal sum score of four mass spectrometry (MS)-identified proteins yielded a sensitivity of 94 % and a specificity of 89 % (AUC = 0.969, 95 % CI = 0.944-0.994) to differentiate AD patients from healthy controls. To bridge the gap between bench and bedside, we developed a high-throughput multiplex protein biochip with great potential for routine AD screening. For convenience and speed of application, this array combines loading control-assisted protein quantification of monoamine oxidase B and tropomyosin 1 with protein-based genotyping for single nucleotide polymorphisms (SNPs) in the apolipoprotein E and glutathione S-transferase omega 1 genes. Based on minimally invasive blood drawing, this innovative protein biochip enables identification of AD patients with an accuracy of 92 % in a single analytical step in less than 4 h.
authors.affiliation: Center of Physiology and Pharmacology, Institute of Physiology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Veitinger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Oehler
authors.forename: Ellen
authors.initials: E
authors.lastname: Umlauf
authors.forename: Roland
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Georg
authors.initials: G
authors.lastname: Schmidt
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
authors.forename: Rita
authors.initials: R
authors.lastname: Babeluk
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.forename: Goran
authors.initials: G
authors.lastname: Mitulovic
authors.forename: Eduard
authors.initials: E
authors.lastname: Rappold
authors.forename: John
authors.initials: J
authors.lastname: Lamont
authors.forename: Maria
authors.initials: M
authors.lastname: Zellner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D001057:Apolipoproteins E; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology; D060825:Cognitive Dysfunction; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008995:Monoamine Oxidase / Q000097:blood / Q000235:genetics; D009483:Neuropsychological Tests; D010641:Phenotype; D040081:Protein Array Analysis / Q000379:methods*; D018709:Statistics, Nonparametric; D014335:Tropomyosin / Q000097:blood / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D001798:Blood Proteins; C490775:TPM1 protein, human; D014335:Tropomyosin; D008995:Monoamine Oxidase; C490476:GSTO1 protein, human; D005982:Glutathione Transferase