| First Author | Shahnur A | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 535 |
| Pages | 25-32 | PubMed ID | 33340762 |
| Mgi Jnum | J:305597 | Mgi Id | MGI:6706054 |
| Doi | 10.1016/j.bbrc.2020.12.036 | Citation | Shahnur A, et al. (2021) A potential defense mechanism against amyloid deposition in cerebellum. Biochem Biophys Res Commun 535:25-32 |
| abstractText | Amyloid-beta (Abeta) 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 Abeta deposition than CTX. It is very important to elucidate the mechanism of suppressing Abeta 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 Abeta deposition in CBL. We observed higher age-dependent elevation of Abeta 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 Abeta in these brain tissues. These data imply that less Abeta deposition in CBL is due to enhanced Abeta clearance rather than altered Abeta production in CBL. To gain insights into Abeta clearance in CBL, we injected fluorescence-labeled Abeta in brain tissues. Importantly diffusion area of fluorescent Abeta in CBL was roughly six-times larger than that in CTX within 2 h of injection. In addition, injected Abeta area in CBL decreased sharply after 24 h and CBL-injected Abeta was robustly detected in deep cervical lymph nodes (DcLNs). In contrast, diffusion area of fluorescent Abeta in CTX was consistent up to 72 h and CTX-injected Abeta was faintly detected in DcLNs. Our data suggest that enhanced Abeta drainage in association with meningeal lymphatic system is responsible for less Abeta deposition in CBL. |
