The Amyloid-Beta Clearance: From Molecular Targets to Glial and Neural Cells

The deposition of amyloid-beta (A beta) plaques in the brain is one of the primary pathological characteristics of Alzheimer's disease (AD). It can take place 20-30 years before the onset of clinical symptoms. The imbalance between the production and the clearance of A beta is one of the major causes of AD. Enhancing A beta clearance at an early stage is an attractive preventive and therapeutic strategy of AD. Direct inhibition of A beta production and aggregation using small molecules, peptides, and monoclonal antibody drugs has not yielded satisfactory efficacy in clinical trials for decades. Novel approaches are required to understand and combat A beta deposition. Neurological dysfunction is a complex process that integrates the functions of different types of cells in the brain. The role of non-neurons in AD has not been fully elucidated. An in-depth understanding of the interactions between neurons and non-neurons can contribute to the elucidation of A beta formation and the identification of effective drug targets. AD patient-derived pluripotent stem cells (PSCs) contain complete disease background information and have the potential to differentiate into various types of neurons and non-neurons in vitro, which may bring new insight into the treatment of AD. Here, we systematically review the latest studies on A beta clearance and clarify the roles of cell interactions among microglia, astroglia and neurons in response to A beta plaques, which will be beneficial to explore methods for reconstructing AD disease models using inducible PSCs (iPSCs) through cell differentiation techniques and validating the applications of models in understanding the formation of A beta plaques. This review may provide the most promising directions of finding the clues for preventing and delaying the development of AD.