Astrocyte–Neuron Interactions in Alzheimer’s Disease

Besides its two defining misfolded proteinopathies-Aβ plaques and tau neurofibrillary tangles-Alzheimer's disease (AD) is an exemplar of a neurodegenerative disease with prominent reactive astrogliosis, defined as the set of morphological, molecular, and functional changes that astrocytes suffer as the result of a toxic exposure. Reactive astrocytes can be observed in the vicinity of plaques and tangles, and the relationship between astrocytes and these AD neuropathological lesions is bidirectional so that each AD neuropathological hallmark causes specific changes in astrocytes, and astrocytes modulate the severity of each neuropathological feature in a specific manner. Here, we will review both how astrocytes change as a result of their chronic exposure to AD neuropathology and how those astrocytic changes impact each AD neuropathological feature. We will emphasize the repercussions that AD-associated reactive astrogliosis has for the astrocyte-neuron interaction and highlight areas of uncertainty and priorities for future research.