A number of cell surface proteins have been reported to act as Aβ receptors. There are age-dependent Aβ isoforms present in the pathological brain, thus accelerating the formation of Aβ plaques. Fibrillar Aβ is the major component of cerebral cortical plaques. The assemblies of oligomers are transient. Oligomers are kinetic intermediates in fibrillar Aβ assembly reactions. Soluble oligomers are considered the most toxic form of Aβ. Aβ with a length of 42 amino acids is one of the most common monomeric fragments that are unstable and readily assemble into metastable oligomers through hydrophobic and hydrogen bonding interactions. With the action of β-secretase in the ectodomain and γ-secretase in intra-membranous locations, APP can be hydrolyzed to produce a residue with 39–43 amino acids, known as an Aβ monomer. Aβ is located in the transmembrane region of APP in neuronal synapses. The amyloid cascade hypothesis was developed as a result of the discovery of the APP gene mutation, which is the first identified gene associated with AD. Aβ alteration over time and space also contributes to the cognitive impairment of AD patients. Extracellular Aβ deposition and neurofibrillary tangles caused by abnormal Tau protein hyperphosphorylation are usually observed in brain tissues of AD patients. The mutation elevates the levels of Aβ monomers by altering the proteolytic way of APP. Patients with familial AD carry mutations in either amyloid precursor protein (APP) or presenilin (PSEN1 or PSEN2). The heritability of early AD is more than 90%. The development of EOAD is associated with multiple genetic factors. EOAD affects 5% of people, with symptoms appearing before 65 years old. Early-onset AD (EOAD) and late-onset AD (LOAD) are the two subgroups of AD based on the age of onset. The global prevalence of AD is 20% and 5% among people over 85 and over 65 years old, respectively. In clinical practice, the patients present memory deficits, cognitive dysfunction, language and visual-spatial impairment, and behavioral dysfunction. This review may provide the most promising directions of finding the clues for preventing and delaying the development of AD.ĪD is a progressive neurodegenerative disease characterized by the deposition of Aβ and the formation of neurofibrillary tangles with hyperphosphorylated Tau protein. Here, we systematically review the latest studies on Aβ clearance and clarify the roles of cell interactions among microglia, astroglia and neurons in response to Aβ 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 Aβ plaques. 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. An in-depth understanding of the interactions between neurons and non-neurons can contribute to the elucidation of Aβ formation and the identification of effective drug targets. The role of non-neurons in AD has not been fully elucidated. Neurological dysfunction is a complex process that integrates the functions of different types of cells in the brain. Novel approaches are required to understand and combat Aβ deposition. Direct inhibition of Aβ production and aggregation using small molecules, peptides, and monoclonal antibody drugs has not yielded satisfactory efficacy in clinical trials for decades. Enhancing Aβ clearance at an early stage is an attractive preventive and therapeutic strategy of AD. The imbalance between the production and the clearance of Aβ is one of the major causes of AD. It can take place 20–30 years before the onset of clinical symptoms. The deposition of amyloid-beta (Aβ) plaques in the brain is one of the primary pathological characteristics of Alzheimer’s disease (AD).
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