Alzheimer’s disease (AD) is the most common age-associated dementia. Many studies have sought to predict cerebral amyloid deposition, the major pathological hallmark of AD, using body fluids such as blood or cerebral spinal fluid (CSF). The use of blood in diagnostic procedures is widespread in medicine; however, existing blood biomarkers for AD remain unreliable. We sought to discover blood biomarkers that discriminate Aβ deposition status in the brain. This study used 107 individuals who were cognitively normal (CN), 107 patients with mild cognitive impairment (MCI), and 40 AD patients with Pittsburg compound B positron emission tomography (PiB-PET) amyloid imaging data available. We found five plasma biomarker candidates via mass spectrometry (MS) based-proteomic analysis and validated these proteins using enzyme-linked immunosorbent assay (ELISA). Our integrated models were highly predictive of brain amyloid deposition, exhibiting 0.871 accuracy with 79% sensitivity and 84% specificity overall, and 0.836 accuracy with 68% sensitivity and 90% specificity in patients with MCI. These results indicated that a combination of proteomic-based blood proteins might be a possible biomarker set for predicting cerebral amyloid deposition.
ACE, angiotensin-converting enzyme; AD, Alzheimer’s disease; ANCOVA, analysis of covariance; ANOVA, analysis of variance; ATRN, attractin; AUC, area under the curve; AZGP1, zinc-alpha-2-glycoprotein precursor; CDH5, vascular endothelial cadherin 5; CN, cognitively normal; CPN2, carboxypeptidase N subunit 2; CSF, cerebrospinal fluid; CV, covariates; DE, differentially expressed; ELISA, enzyme-linked immunosorbent assay; ERAP2, endoplasmic reticulum aminopeptidase 2; IRB, Institutional Review Board; KBASE, Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease; LGALS3BP, galectin-3-binding protein; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; MRI, magnetic resonance imaging; MS, mass spectrometry; NRI, net reclassification improvement; PiB-PET, Pittsburg compound B positron emission tomography; POSTN, periostin; ROC, receiver operating characteristic; RR, relative risk; TMT, tandem mass tag; VWF, von Willebrand factor; α2M, alpha-2-macroglobulin
Keywords : Alzheimer’s disease; Proteomics; PiB-PET; Plasma biomarker; TMT; Cerebral amyloid deposition