A platelet protein biochip rapidly detects an Alzheimer’s disease-specific phenotype

• Published in: Acta neuropathologica Vol. 128; no. 5; pp. 665 - 677
• Main Authors: Veitinger, Michael, Oehler, Rudolf, Umlauf, Ellen, Baumgartner, Roland, Schmidt, Georg, Gerner, Christopher, Babeluk, Rita, Attems, Johannes, Mitulovic, Goran, Rappold, Eduard, Lamont, John, Zellner, Maria
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2014; Springer; Springer Nature B.V
• Subjects: Activities of daily living; Aged; Aged, 80 and over; Algorithms; Alzheimer Disease - blood; Alzheimer Disease - complications; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoproteins E; Biomarkers; Blood; Blood platelets; Blood Platelets - metabolism; Blood Proteins - metabolism; Cognition Disorders - etiology; Cognitive Dysfunction; Female; Genetic aspects; Glutathione transferase; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Humans; Laboratories; Male; Mass Spectrometry; Medical examination; Medical imaging; Medicine; Medicine & Public Health; Monoamine oxidase; Monoamine Oxidase - blood; Monoamine Oxidase - genetics; Muscle proteins; Neuropsychological Tests; Neurosciences; Original Paper; Pathology; Phenotype; Protein Array Analysis - methods; Single nucleotide polymorphisms; Statistics, Nonparametric; Tropomyosin - blood; Tropomyosin - genetics; United Kingdom > UK; Austria; Biomarker; Diagnosis; Alzheimer’s disease; Blood platelets; Hematologic test; Multiplex protein biochip
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-014-1341-8

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.