RESUMEN
Amyloid-ß (Aß) 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 Aß deposition than CTX. It is very important to elucidate the mechanism of suppressing Aß 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 Aß deposition in CBL. We observed higher age-dependent elevation of Aß 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 Aß in these brain tissues. These data imply that less Aß deposition in CBL is due to enhanced Aß clearance rather than altered Aß production in CBL. To gain insights into Aß clearance in CBL, we injected fluorescence-labeled Aß in brain tissues. Importantly diffusion area of fluorescent Aß in CBL was roughly six-times larger than that in CTX within 2 h of injection. In addition, injected Aß area in CBL decreased sharply after 24 h and CBL-injected Aß was robustly detected in deep cervical lymph nodes (DcLNs). In contrast, diffusion area of fluorescent Aß in CTX was consistent up to 72 h and CTX-injected Aß was faintly detected in DcLNs. Our data suggest that enhanced Aß drainage in association with meningeal lymphatic system is responsible for less Aß deposition in CBL.
