Role of Microglia and Astrocytes in Alzheimer’s Disease: From Neuroinflammation to Ca(2+) Homeostasis Dysregulation

Alzheimer’s disease (AD) is the most common form of dementia worldwide, with a complex, poorly understood pathogenesis. Cerebral atrophy, amyloid-β (Aβ) plaques, and neurofibrillary tangles represent the main pathological hallmarks of the AD brain. Recently, neuroinflammation has been recognized as a prominent feature of the AD brain and substantial evidence suggests that the inflammatory response modulates disease progression. Additionally, dysregulation of calcium (Ca(2+)) homeostasis represents another early factor involved in the AD pathogenesis, as intracellular Ca(2+) concentration is essential to ensure proper cellular and neuronal functions. Although growing evidence supports the involvement of Ca(2+) in the mechanisms of neurodegeneration-related inflammatory processes, scant data are available on its contribution in microglia and astrocytes functioning, both in health and throughout the AD continuum. Nevertheless, AD-related aberrant Ca(2+) signalling in astrocytes and microglia is crucially involved in the mechanisms underpinning neuroinflammatory processes that, in turn, impact neuronal Ca(2+) homeostasis and brain function. In this light, we attempted to provide an overview of the current understanding of the interactions between the glia cells-mediated inflammatory responses and the molecular mechanisms involved in Ca(2+) homeostasis dysregulation in AD.