title: Part of membrane-bound Abeta exists in rafts within senile plaques in Tg2576 mouse brain.
abstract: To clarify whether rafts are the site of abnormal amyloid beta protein (Abeta) deposition, we examined the ultrastructural localization of both flotillin-1 (pre-embedding) and Abeta (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 Abeta was predominantly observed on plasma membranes of small processes in diffuse plaques. Non-fibrillar and fibrillar Abeta 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 Abeta42 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 Abeta exists in lipid rafts within senile plaques, and suggests that rafts could be one of the sites for initial Abeta deposition.
authors.affiliation: Gunma University School of Health Sciences, 3-39-15 Showa-machi, 371-8514 Maebashi, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Kokubo
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Iwata
authors.forename: J Bernd
authors.initials: JB
authors.lastname: Helms
authors.forename: Rumi
authors.initials: R
authors.lastname: Shinohara
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002462:Cell Membrane; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron / Q000379:methods; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000145:classification* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C106354:flotillins