Dynein dysfunction disrupts β-amyloid clearance in astrocytes through endocytic disturbances.

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 beta-amyloid (A beta) 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, A beta accumulates in these enlarged endosomes. RNA interference studies have shown that dynein dysfunction reproduces astroglial endocytic pathology and disrupts A beta clearance in astrocytes through endocytic disturbances. These findings suggest that endocytic disturbances can alter astroglial functions and may also be involved in age-dependent A beta pathology.