The inability of individual neurons to compensate for aging-related damage leads to a gradual loss of functional plasticity in the brain accompanied by progressive impairment in learning and memory. Whereas this loss in neuroplasticity is gradual during normal aging, in neurodegenerative diseases such as Alzheimer’s disease (AD), this loss is accelerated dramatically, leading to the incapacitation of patients within a decade of onset of cognitive symptoms. The mechanisms that underlie this accelerated loss of neuroplasticity in AD are still not completely understood. While the progressively increasing proteinopathy burden, such as amyloid β (Aβ) plaques and tau tangles, definitely contribute directly to a neuron’s functional demise, the role of non-neuronal cells in controlling neuroplasticity is slowly being recognized as another major factor. These non-neuronal cells include astrocytes, microglia, and oligodendrocytes, which through regulating brain homeostasis, structural stability, and trophic support, play a key role in maintaining normal functioning and resilience of the neuronal network. It is believed that chronic signaling from these cells affects the homeostatic network of neuronal and non-neuronal cells to an extent to destabilize this harmonious milieu in neurodegenerative diseases like AD. Here, we will examine the experimental evidence regarding the direct and indirect pathways through which astrocytes and microglia can alter brain plasticity in AD, specifically as they relate to the development and progression of tauopathy. In this review article, we describe the concepts of neuroplasticity and glial plasticity in healthy aging, delineate possible mechanisms underlying tau-induced plasticity dysfunction, and discuss current clinical trials as well as future disease-modifying approaches.

单个神经元无法补偿与衰老相关的损伤，导致大脑功能可塑性逐渐丧失，并伴随着学习和记忆的逐步损害。在正常的衰老过程中，神经可塑性的丧失是逐渐的，而在诸如阿尔茨海默氏病（AD）的神经退行性疾病中，这种丧失的速度大大加快，导致患者在认知症状发作后的十年内丧失了能力。尚不清楚AD加速这种神经可塑性丧失的基础机制。虽然逐渐增加的蛋白质病负担（例如淀粉样蛋白β（Aβ）斑块和tau缠结）无疑直接导致了神经元的功能衰竭，但非神经细胞在控制神经可塑性中的作用逐渐被认为是另一个主要因素。这些非神经元细胞包括星形胶质细胞，小胶质细胞和少突胶质细胞，它们通过调节脑稳态，结构稳定性和营养支持在维持神经元网络的正常功能和弹性中起关键作用。据信，来自这些细胞的慢性信号传导在一定程度上影响神经元和非神经元细胞的稳态网络，从而在诸如AD的神经退行性疾病中破坏该和谐环境。在这里，我们将研究有关星形胶质细胞和小胶质细胞可以改变AD中大脑可塑性的直接和间接途径的实验证据，特别是因为它们与tauopathy的发展和进程有关。在这篇评论文章中，我们描述了健康衰老中神经可塑性和神经胶质可塑性的概念，