Amyloid-β (Aβ) peptides can form protease-resistant aggregates within and outside of neurons. Accumulation of these aggregates is a hallmark of Alzheimer’s disease (AD) neuropathology and contributes to devastating cognitive deficits associated with this disorder. The primary etiological factor for Aβ aggregation is either an increase in Aβ production or a decrease in its clearance. Aβ is produced by the sequential activity of β- and γ-secretase on the amyloid precursor protein (APP) and the clearance is mediated by chaperone-mediated mechanisms. The Aβ aggregates vary from soluble monomers and oligomers to insoluble senile plaques. While excess intraneuronal oligomers can transduce neurotoxic signals into neurons causing cellular defects like oxidative stress and neuroepigenetic mediated transcriptional dysregulation, extracellular senile plaques cause neurodegeneration by impairing neural membrane permeabilization and cell signaling pathways. Paradoxically, senile plaque formation is hypothesized to be an adaptive mechanism to sequester excess toxic soluble oligomers while leaving native functional Aβ levels intact. This hypothesis is strengthened by the absence of positive outcomes and side effects from immunotherapy clinical trials aimed at complete Aβ clearance, and support beneficial physiological roles for native Aβ in cellular function. Aβ has been shown to modulate synaptic transmission, consolidate memory, and protect against excitotoxicity. We discuss the current understanding of beneficial and detrimental roles for Aβ in synaptic function and epigenetic gene control and the future promising prospects of early therapeutic interventions aimed at mediating Aβ induced neuroepigenetic and synaptic dysfunctions to delay AD onset.

淀粉样β（Aβ）肽可以在神经元内外形成蛋白酶抗性聚集体。这些聚集体的积累是阿尔茨海默氏病（AD）神经病理学的标志，并有助于破坏与该疾病相关的认知缺陷。Aβ聚集的主要病因是Aβ产量增加或清除率降低。Aβ是由β-和γ-分泌酶对淀粉样前体蛋白（APP）的顺序活性产生的，清除率是由伴侣蛋白介导的机制介导的。Aβ聚集体从可溶性单体和低聚物到不溶性老年斑不等。虽然过多的神经内神经内低聚物可以将神经毒性信号转化为神经元，从而导致细胞缺陷，例如氧化应激和神经表观遗传介导的转录失调，细胞外老年斑通过损害神经膜通透性和细胞信号传导途径引起神经变性。矛盾的是，衰老斑块的形成被认为是一种螯合过量有毒可溶性寡聚体而又保持天然功能性Aβ水平不变的适应性机制。缺乏针对完全Aβ清除的免疫疗法临床试验的阳性结果和副作用，并支持天然Aβ在细胞功能中的有益生理作用，这一假设得到了加强。Aβ已显示可调节突触传递，巩固记忆并防止兴奋性毒性。