Amyloid-β protein (Aβ) is the main component of senile plaques in the brains of Alzheimer disease (AD) patients. Aβ is proteolytically derived from amyloid-β precursor protein by β- and γ-secretases. Secreted Aβ is then eliminated from the central nervous system by multiple clearance mechanisms, including phagocytosis, immune responses, and proteolytic degradation. These dynamic metabolic processes, which are referred to as Aβ economy, regulate steady-state brain Aβ levels. Familial AD-linked genetic mutations augment the production and aggregation of Aβ. In contrast, rare genetic variants that reduce Aβ production were protective against AD. Moreover, decreased Aβ clearance has been demonstrated in sporadic AD patients, suggesting that dysregulation of Aβ economy contributes to the development of AD. Thus, several approaches to inhibit the production as well as to enhance the clearance of Aβ have been investigated as potential therapeutics against AD. In this manuscript, we introduce the molecules and cellular mechanisms involved in the regulation of Aβ economy and discuss the current understanding of these processes in the development of therapeutics against AD. J. Cell. Biochem. 118: 4183-4190, 2017. © 2017 Wiley Periodicals, Inc.
Keywords: ALZHEIMER DISEASE; AMYLOID; GLIA; NEURODEGENERATION; PROTEASE.
© 2017 Wiley Periodicals, Inc.