Part of membrane-bound Abeta exists in rafts within senile plaques in Tg2576 mouse brain.
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.
Kokubo
Hideko
H
Gunma University School of Health Sciences, 3-39-15 Showa-machi, 371-8514 Maebashi, Japan.
Saido
Takaomi C
TC
Iwata
Nobuhisa
N
Helms
J Bernd
JB
Shinohara
Rumi
R
Yamaguchi
Haruyasu
H
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
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C106354:flotillins