The Uptake, Trafficking And Clearance Of Aβ In Microglia

Alzheimer’s disease(AD), the most prominent cause of senile dementia, is clinically characterized by the extracellular deposition of beta-amyloid (Aβ) and the intracellular neurofibrillary tangles. It has been well accepted that AD pathogenesis arises from perturbation in the homeostasis of Aβ in the brain. Aβ is normally produced at high levels in the brain and cleared in an equivalent rate. Thus, even a moderate decrease in the clearance leads to the accumulation of Aβ and subsequent amyloid deposition. Evidence indicates that soluble Aβ species, rather than insoluble ones, are the most toxic forms of Aβ. Microglia is tissue macrophages in the central nervous system (CNS) and has been shown to play major roles in internalization and degradation of Aβ. Various studies have shown that microglia mediate the clearance of soluble Microglia is tissue macrophages in the central nervous system (CNS) and has been shown to play major roles in internalization and degradation of Aβ. through fluid phase macropinocytosis. Here we confirm that microglia can efficiently take up a large amount of Aβ, and after internalization, sAβ can rapidly reach lysosome for degradation.ln addition, we show that BV-2microglia cells can internalize more Aβ and in a more quickly manner than neuroblastoma N2a cells. Moreover, internalized sAβ can reach lysosome faster and degrade more in BV-2cells than in N2a cells.Our study reveals the role of microglia in mediating Aβ degradation and suggests that microglia contributes to the progression of AD.thus providing additional information for understanding the mechanism underlying the pathogenesis of AD.