MFG-E8, a potential blood biomarker for Alzheimer's disease carrying ApoE4 genotype

Aim: We have previously identified Milk fat globule-EGF factor 8 protein (MFG-E8) as a novel biomarker for Alzheimer's disease (AD) using a mouse model. In this study,we investigated the potential of MFG-E8 as a plasma biomarker. Methods: We established an ELISA system using two monoclonal antibody clones against recombinant human MFG-E8 to measure plasma MFG-E8. Plasma samples (183 samples of Alzheimer's disease (AD) patients, 51 of dementia with Lewy bodies (DLB), and 420 of age-matched healthy control (HC)) were obtained. Results: The plasma level of MFG-E8 tended to be increased in AD and was significantly higher in AD patients with ApoE4 genotype, compared with HC. On the other hand, the plasma levels of MFG-E8 were comparable between AD patients without ApoE4 genotype and HC. Plasma MFG-E8 levels were comparable regardless of ApoE4 genotype in HC. The plasma MFG-E8 of DLB with ApoE4 genotype tended to be increased, but was not significant compared to HC. There was a gender-dependent difference in plasma MFG-E8. The plasma MFG-E8 was significantly higher in males than in females in both AD and HC, and tended to be higher in males than in females in DLB. It was found that medication for dyslipidemia caused a decrease in the plasma MFG-E8 in HC. Conclusions: MFG-E8 is a potential plasma biomarker for AD carrying ApoE4 genotype.