Apolipoprotein C-III is an amyloid-β-binding protein and an early marker for Alzheimer's disease

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.