Part of membrane-bound Aβ exists in rafts within senile plaques in Tg2576 mouse brain

Abstract

To clarify whether rafts are the site of abnormal amyloid β protein (Aβ) deposition, we examined the ultrastructural localization of both flotillin-1 (pre-embedding) and Aβ (post-embedding) in Tg2576 mouse brains. After observing the exact areas of senile plaques by reflection contrast microscopy, we observed these same plaques under an electron microscope. Membrane-bound Aβ was predominantly observed on plasma membranes of small processes in diffuse plaques. Non-fibrillar and fibrillar Aβ was increased in primitive plaques, and the fibrillar form was predominant in mature plaques. The number of flotillin-1-positive rafts per field in mature plaques was prominently less than those outside of the plaques, in diffuse plaques and in primitive plaques. The colocalization of flotillin-1 with Aβ42 appeared approximately 10% of flotillin-1-positive rafts within senile plaques, while there was no colocalization found outside of the plaques. This study ultrastructurally demonstrated that part of membrane-bound Aβ exists in lipid rafts within senile plaques, and suggests that rafts could be one of the sites for initial Aβ deposition.