P011 - A POTENTIAL DEFENSE MECHANISM AGAINST AMYLOID DEPOSITION IN CEREBELLUM
Abstract
Aims
Senile plaques are observed mainly in cerebral cortex (CX), but less in cerebellum (CB). Tg2576 mice also exhibit less Aβ deposition in CB, although APP is overexpressed under the control of prion promoter. APPNL-G-F KI mice also show less Aβ deposition in CB, despite the fact that these mice produce aggregation-prone arctic Aβ42 in whole brain. In this study, we explored to figure out the potential mechanism preventing Aβ deposition in CB.
Methods
(1) In order to compare levels of Aβ between CX and CB, we performed microdialysis experiments on 4-month old APPNL-G-F KI mice. (2) We performed stereotactic injection of HiLyte Fluor555-labeled Aβ42 into brain tissues and examined Aβ diffusion and clearance. (3) We examined the presence of the labeled Aβ42 in deep cervical lymph nodes (DcLNs) as one of drainage routes.
Results
(1) We detected no significant difference in ISF Aβ level between CX and CB. (2) Aβ diffusion area in CB was roughly three-times larger than that in CX right after injection. However, we observed 60% decrease in the Aβ diffusion area in CB after 72 h, while that of CX unchanged. (3) Aβ injected into CB was found in DcLNs within 2 h, while that in CX was faint.
Conclusions
The level of ISF Aβ in CB is equivalent to that in CX. However, Aβ diffusion and clearance rates in CB is higher than those in CX, which leads to less Aβ deposition in CB.
