Microglia receptors and their implications in the response to amyloid β for Alzheimer's disease pathogenesis

Alzheimer's disease (AD) is a major public health problem with substantial economic and social impacts around the world. The hallmarks of AD pathogenesis include deposition of amyloid beta (A beta), neurofibrillary tangles, and neuroinflammation. For many years, research has been focused on A beta accumulation in senile plaques, as these aggregations were perceived as the main cause of the neurodegeneration found in AD. However, increasing evidence suggests that inflammation also plays a critical role in the pathogenesis of AD. Microglia cells are the resident macrophages of the brain and act as the first line of defense in the central nervous system. In AD, microglia play a dual role in disease progression, being essential for clearing A beta deposits and releasing cytotoxic mediators. A beta activates microglia through a variety of innate immune receptors expressed on these cells. The mechanisms through which amyloid deposits provoke an inflammatory response are not fully understood, but it is believed that these receptors cooperate in the recognition, internalization, and clearance of A beta and in cell activation. In this review, we discuss the role of several receptors expressed on microglia in A beta recognition, uptake, and signaling, and their implications for AD pathogenesis.