Impaired axonal transport may promote pathogenesis in neurodegenerative disorders, such as Alzheimer's disease (AD). We previously showed that tau, amyloid precursor protein (APP), and intracellular amyloid beta-protein (Abeta) accumulate in the nerve-ending fraction of aged monkey brains, perhaps because of impaired axonal transport. In the present study, we assessed age-related changes of axonal transport motor proteins in aged monkey brains. Western blotting showed that kinesin, dynein, and dynactin (DYN) localizations dramatically changed with aging, and dynein level in nerve-ending fractions increased significantly. Coimmunoprecipitation analyses showed that DYN-dynein intermediate chain (DIC) interactions decreased, suggesting that age-related attenuation of this interaction may cause the impairment of dynein function. Moreover, RNAi-induced down-regulation of DIC in human neuroblastoma cells caused endogenous tau and APP to accumulate, and their subcellular localizations were also affected. Our findings suggest that aging attenuates DYN-DIC interaction, representing one of the risk factors for age-related impaired dynein function and even for accumulation of disease proteins.