A potential defense mechanism against amyloid deposition in cerebellum.

Amyloid-β (Aβ) is the major component of senile plaques in Alzheimer's disease (AD) brains. Senile plaques are generally observed in cerebral cortex (CTX) rather than cerebellum (CBL) in AD patients. However, it is not clear why CBL has less Aβ deposition than CTX. It is very important to elucidate the mechanism of suppressing Aβ deposition in CBL, because it contributes to understanding of not only AD pathogenesis but also prevention and cure of AD. In this study, we explored to figure out the potential mechanism of reducing Aβ deposition in CBL. We observed higher age-dependent elevation of Aβ level in CTX rather than CBL of human APP knock-in AD model mice, although we detected no significant differences in the levels of interstitial fluid Aβ in these brain tissues. These data imply that less Aβ deposition in CBL is due to enhanced Aβ clearance rather than altered Aβ production in CBL. To gain insights into Aβ clearance in CBL, we injected fluorescence-labeled Aβ in brain tissues. Importantly diffusion area of fluorescent Aβ in CBL was roughly six-times larger than that in CTX within 2 h of injection. In addition, injected Aβ area in CBL decreased sharply after 24 h and CBL-injected Aβ was robustly detected in deep cervical lymph nodes (DcLNs). In contrast, diffusion area of fluorescent Aβ in CTX was consistent up to 72 h and CTX-injected Aβ was faintly detected in DcLNs. Our data suggest that enhanced Aβ drainage in association with meningeal lymphatic system is responsible for less Aβ deposition in CBL. • Less Aβ deposition in cerebellum reflects the less amount of Aβ than that in cerebral cortex. • The Aβ production level in cerebellum is equivalent to that in cerebral cortex. • Aβ diffusion and drainage is enhanced in cerebellum compared to cerebral cortex. • Aβ injected in cerebellum is drained into deep cervical lymph nodes much faster than that in cerebral cortex. [ABSTRACT FROM AUTHOR]