L-3-n-Butylphthalide Effectively Improves the Glymphatic Clearance and Reduce Amyloid-ß Deposition in Alzheimer's Transgenic Mice.

ABSTRACT

Amyloid-ß (Aß) deposit in the parenchyma is a major characteristic in Alzheimer's disease (AD), and the impaired glymphatic clearance contributes to the Aß accumulation. It was reported that L-3-n-butylphthalide (NBP) showed the potential neuroprotective effect in the rodent models of AD. The effects of NBP on the glymphatic system were explored in this study. In the wild-type mice, both CSF tracer influx and perivascular drainage increased after NBP treatment compared with vehicle treatment. Moreover, NBP promoted the perivascular drainage of Aß via increased cerebral pulsation, which could be inhibited by propranolol. Then, we studied the potential of 3-month NBP treatment on Aß deposits in 8-month-old APP/PS1 transgenic mice. NBP daily treatments remarkably improved cognitive behavior in Morris water maze. Furthermore, NBP could reduce Aß deposition and decrease parenchymal Aß levels. In addition, NBP markedly improved the perivascular AQP4 localization. Our results indicated that NBP could enhance the glymphatic clearance and reduce parenchymal Aß deposit in the APP/PS1 mice, suggesting that it may have potential in the treatment of AD.