Affiliations: [a] Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan | [b] Alzheimer Disease Research Center, National Cheng Kung University, Tainan, Taiwan | [c] Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan | [d] Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan | [e] Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan | [f] Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan
Correspondence:
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Correspondence to: Dr. Ming-Chyi Pai, Department of Neurology, National Cheng Kung University. 1 Ta Hsueh Road, Tainan 70101, Taiwan. Tel.: +886 6 2353535/Ext. 5534; E-mail: pair@mail.ncku.edu.tw; Dr. Yu-Min Kuo, Department of Cell Biology and Anatomy, National Cheng Kung University. 1 Ta Hsueh Road, Tainan 70101, Taiwan. Tel.: +886 6 2353535/Ext. 5294; Fax: +886 6 2093007; E-mail: kuoym@mail.ncku.edu.tw.
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.
Keywords: Amyloid-β binding protein, apolipoprotein, biomarker, family history, plasma
