title: Dynein dysfunction disrupts β-amyloid clearance in astrocytes through endocytic disturbances.
abstract: We showed previously that aging attenuates the interaction between dynein-dynactin complexes in cynomolgus monkey brain and that dynein dysfunction reproduces age-dependent endocytic disturbances, resulting in intracellular β-amyloid (Aβ) accumulation, synaptic vesicle transport deficits, and neuritic swelling. It remains unclear whether such endocytic disturbances also occur in glial cells. Here, we show that endocytic pathology, such as intracellular accumulation of enlarged endosomes, occurs in astrocytes of aged monkey brains. Also, Aβ accumulates in these enlarged endosomes. RNA interference studies have shown that dynein dysfunction reproduces astroglial endocytic pathology and disrupts Aβ clearance in astrocytes through endocytic disturbances. These findings suggest that endocytic disturbances can alter astroglial functions and may also be involved in age-dependent Aβ pathology.
authors.affiliation: aSection of Cell Biology and Pathology, Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Aichi bTsukuba Primate Research Center, National Institute of Biomedical Innovation cThe Corporation for Production and Research of Laboratory Primates, Tsukuba, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kimura
authors.forename: Sachi
authors.initials: S
authors.lastname: Okabayashi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Ono
mesh_terms: D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000166:cytology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008252:Macaca fascicularis; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D000072159:Dynactin Complex; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D004398:Dyneins