title: The role of microglia in amyloid clearance from the AD brain.
abstract: Alzheimer's disease (AD), the most prominent cause of senile dementia, is clinically characterized by the extracellular deposition of beta-amyloid (Abeta) and the intracellular neurofibrillary tangles. It has been well accepted that AD pathogenesis arises from perturbation in the homeostasis of Abeta in the brain. Abeta 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 Abeta and subsequent amyloid deposition. Microglia are the tissue macrophages in the central nervous system (CNS) and have been shown to play major roles in internalization and degradation of Abeta. Abeta exists in the brain both in soluble and in fibrillar forms. Microglia interact with these two forms of Abeta in different ways. They take up soluble forms of Abeta through macropinocytosis and LDL receptor-related proteins (LRPs) mediated pathway. Fibrillar forms of Abeta interact with the cell surface innate immune receptor complex, initiating intracellular signaling cascades that stimulate phagocytosis. Inflammatory responses influence the activation status of microglia and subsequently regulate their ability to take up and degrade Abeta. ApoE and its receptors have been shown to play critical roles in these processes. In this review, we will explore the mechanisms that microglia utilize to clear Abeta and the effectors that modulate the processes.
authors.affiliation: School of Medicine, Case Western Reserve University, SOM E649, 10900 Euclid Avenue, Cleveland, OH 44106-4928, USA. cydlee@case.edu
authors.forename: C Y Daniel
authors.initials: CY
authors.lastname: Lee
authors.forename: Gary E
authors.initials: GE
authors.lastname: Landreth
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D001057:Apolipoproteins E / Q000502:physiology; D001921:Brain / Q000166:cytology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*
chemical_list: D000682:Amyloid; D001057:Apolipoproteins E