Medicine and Health Sciences Commons^™

Microglia Prevent Beta-Amyloid Plaque Formation In The Early Stage Of An Alzheimer's Disease Mouse Model With Suppression Of Glymphatic Clearance, Weixi Feng, Yanli Zhang, Ze Wang, Hanrong Xu, Ting Wu, Charles Marshall, Junying Gao, Ming Xiao

Physical Therapy Faculty Publications

BACKGROUND: Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer's disease (AD) are currently unknown.

METHODS: Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4^−/−) mice, and AQP4^−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein …