Milk fat globule-EGF-factor 8 is induced from neuronal cells upon stimulation of Aβ oligomer and specifi cally localizes in amyloid plaques in the brain of mouse model for Alzheimer’s disease.

Amyloid β (Aβ), a proteolytic product of amyloid precursor protein, plays an important role for apoptosis of neuronal cells and closely links to Alzheimer’s disease, though a detailed molecular mechanism remains studied. This is partly due to a lack of molecular information on affected neurons by Aβ peptides. To get more insights of this characteristic condition, we took an advantage of proteomic approach studying culture supernatant of neuronal cells treated with Aβ peptide oligomer and screened proteins preferentially bound for phosphatidylserine (PS), an acidic phospholipid expressed on outer leafl ets of apoptotic cell membranes, by employing a modifi ed liposome. Upon stimulation by Aβ, a number of proteins were detected in culture supernatant including milk fat globule-EGF-factor 8 (MFG-E8). MFG-E8 is found to be increased in the supernatant and preferentially localized in cytoplasm of neurons but not in glial cells with Aβ treatment in cultures. Quite interestingly, localization of MFG-E8 is apparently detected in cored plaques of mouse brain of Tg2576, a model for Alzheimer’s disease carrying the Swedish mutation of APP (APPK670N, M671L). The distribution of MFG-E8 is found to be limited inside of plaques and surrounded by Aβ in all plaques examined. This expression is barely detectable in control mice brain. Signifi cant increase of MFG-E8 is further observed in plasma of Alzheimer’s disease patients. Collectively, MFG-E8 is a new component of amyloid plaques and seemed to be closely linked with Aβ primed neuronal pathology. The specifi c expression of MFG-E8 in amyloid plaques may suggest an important role of apoptotic process controlled by this particular molecule. (255 words)