Abstract
Alzheimer’s disease (AD), the most prominent cause of senile dementia, is clinically characterized by the extracellular deposition of β-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. Microglia are the tissue macrophages in the central nervous system (CNS) and have been shown to play major roles in internalization and degradation of Aβ. Aβ exists in the brain both in soluble and in fibrillar forms. Microglia interact with these two forms of Aβ in different ways. They take up soluble forms of Aβ through macropinocytosis and LDL receptor-related proteins (LRPs) mediated pathway. Fibrillar forms of Aβ 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 Aβ. 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 Aβ and the effectors that modulate the processes.
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Lee, C.Y.D., Landreth, G.E. The role of microglia in amyloid clearance from the AD brain. J Neural Transm 117, 949–960 (2010). https://doi.org/10.1007/s00702-010-0433-4
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DOI: https://doi.org/10.1007/s00702-010-0433-4