Endosomal accumulation of GM1 ganglioside-bound amyloid beta-protein in neurons of aged monkey brains.
We performed an immunohistochemical analysis of the GM1 ganglioside-bound amyloid beta-protein (GAbeta), an endogenous seed of Alzheimer amyloids, in sections of cerebral cortices of cynomolgus monkeys of different ages from 4 to 36 years old. Here, we show that neuronal GAbeta immunostaining significantly increases in the sections obtained from animals at ages below 19 years, even without senile plaque formation, and that GAbeta accumulation exclusively occurs in organelles involved in the endocytic pathway, including early, late, and recycling endosomes, not in those involved in the secretory pathway. Together with previous findings that Abeta generation likely occurs in early endosomes and that GM1 accumulation in early endosomes is induced by endocytic pathway abnormalities, our results provide further evidence that endosomes are intimately involved in the Abeta-associated pathology of Alzheimer's disease.
Kimura
Nobuyuki
N
Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Hachimandai, Tsukuba-shi, Ibaraki, Japan. kimura@nibio.go.jp
Yanagisawa
Katsuhiko
K
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism* / Q000473:pathology; D005677:G(M1) Ganglioside / Q000378:metabolism*; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D016229:Amyloid beta-Peptides; D005677:G(M1) Ganglioside