Lai Aaron Y, McLaurin Joanne
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, CA M5S 1A2, Canada.
Future Neurol. 2012 Mar 1;7(2):165-176. doi: 10.2217/fnl.12.6.
Accumulation of senile plaques consisting of amyloid-β peptide (Aβ) aggregates is a prominent pathological feature in Alzheimer's disease. Effective clearance of Aβ from the brain parenchyma is thought to regulate the development and progression of the disease. Macrophages in the brain play an important role in Aβ clearance by a variety of phagocytic and digestive mechanisms. Subpopulations of macrophages are heterogeneous such that resident microglia in the parenchyma, blood macrophages infiltrating from the periphery, and perivascular macrophages residing along cerebral vessels make functionally distinct contributions to Aβ clearance. Despite phenotypic similarities between the different macrophage subsets, a series of in vivo models have been derived to differentiate their relative impacts on Aβ dynamics as well as the molecular mechanisms underlying their activities. This review discusses the key findings from these models and recent research efforts to selectively enhance macrophage clearance of Aβ.
由淀粉样β肽（Aβ）聚集体组成的老年斑积累是阿尔茨海默病的一个突出病理特征。从脑实质有效清除Aβ被认为可调节该疾病的发展和进程。大脑中的巨噬细胞通过多种吞噬和消化机制在Aβ清除中发挥重要作用。巨噬细胞亚群具有异质性，使得实质中的常驻小胶质细胞、从外周浸润的血液巨噬细胞以及沿脑血管驻留的血管周围巨噬细胞对Aβ清除做出功能上不同的贡献。尽管不同巨噬细胞亚群之间存在表型相似性，但已经建立了一系列体内模型来区分它们对Aβ动态的相对影响以及其活动背后的分子机制。本综述讨论了这些模型的关键发现以及最近为选择性增强巨噬细胞对Aβ的清除所做的研究努力。
