title: Apolipoprotein C-III is an amyloid-β-binding protein and an early marker for Alzheimer's disease.
abstract: It has been demonstrated that peripheral injection of anti-amyloid-β (Aβ) antibodies to patients with Alzheimer's disease (AD) and AD transgenic mice facilitate Aβ clearance. We hypothesized that peripheral circulating Aβ-binding proteins also possess the ability to enhance Aβ clearance and the levels of circulating Aβ-binding proteins could serve as early AD biomarkers. Circulating Aβ-binding proteins were isolated from plasma and identified by LC-MS/MS. Their levels were compared among non-demented individuals without AD family history (ND), with AD family history (ND-FH), and patients with mild AD. The results showed that most of the identified Aβ-binding proteins were apolipoproteins, i.e., apoA-I, apoB-100, apoC-III, and apoE. Aβ bound preferentially to apoA-I-enriched HDL, followed by apoC-III- and apoE-enriched VLDL, and bound less favorably to apoB-100-enriched LDL. Levels of apoA-I were reduced in AD patients and could be used to discriminate AD from ND groups (AUC: 0.93); whereas levels of apoC-III were reduced in both ND-FH and AD groups and could be used to differentiate ND-FH from ND individuals (AUC: 0.81). Both the levels of apoA-1 and apoC-III positively correlated with CASI and MMSE scores. In conclusion, these results suggest that plasma apoA-I could be a sensitive AD biomarker and individuals with low plasma levels of apoC-III are at risk for AD.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yao-Hsiang
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan Alzheimer Disease Research Center, National Cheng Kung University, Tainan, Taiwan Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuen-Jer
authors.initials: KJ
authors.lastname: Tsai
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chu-Wan
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan Alzheimer Disease Research Center, National Cheng Kung University, Tainan, Taiwan Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shu-Chu
authors.initials: SC
authors.lastname: Shiesh
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Chen
authors.affiliation: Alzheimer Disease Research Center, National Cheng Kung University, Tainan, Taiwan Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ming-Chyi
authors.initials: MC
authors.lastname: Pai
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan Alzheimer Disease Research Center, National Cheng Kung University, Tainan, Taiwan Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Kuo
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000097:blood*; D016632:Apolipoprotein A-I / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011485:Protein Binding; D012372:ROC Curve; D018709:Statistics, Nonparametric
chemical_list: D016229:Amyloid beta-Peptides; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III
keywords: Amyloid-β binding protein; apolipoprotein; biomarker; family history; plasma