MFG-E8, A Novel Biomarker for Alzheimer’s Disease and Its Amyloidotic Feature

Abstract

Biomarker study on dementia has developed and the most reliable fluid markers are amyloid peptide (Aβ), TAU, and phosphorylated TAU detected in cerebrospinal fluid (CSF). We have focused on novel Alzheimer’s disease (AD) biomarker candidates (annexin A5 and Milk fat globule-EGF factor 8 protein [MFG-E8]), Ca2+ and phospholipid binding properties, which were elevated in the neuronal cell culture medium by Aβ42 treatment. We have previously reported annexin A5 as an AD biomarker. In this chapter, we focused on MFG-E8. An immunohistochemical study using AD mouse model (APP/PS1) brains revealed characteristic distributions of the staining with anti-MFG-E8 antibody. Anti-MFG-E8 antibody staining was detected in the core regions of the anti-Aβ-antibody stained plaques in 20 weeks old and older APP/PS1 mice, while no staining was observed in control (wild mouse) and anti-Aβ-antibody staining was detected outside of it. The volume of the staining was augmented with advancing age. It was further revealed that the MFG-E8 protein changed to amyloidotic features over time from the Congo red spectral peak shift and electron microscopic study in vitro. As the emergence of senile plaque takes a long time, MFG-E8 present in the plaque might be in an amyloidotic form. From these results, MFG-E8 is a novel biomarker candidate for AD.