Role of Microglia and Astrocytes in Alzheimer's Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation

Cells. 2022 Sep 1;11(17):2728. doi: 10.3390/cells11172728.


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 (Ca2+) homeostasis represents another early factor involved in the AD pathogenesis, as intracellular Ca2+ concentration is essential to ensure proper cellular and neuronal functions. Although growing evidence supports the involvement of Ca2+ 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 Ca2+ signalling in astrocytes and microglia is crucially involved in the mechanisms underpinning neuroinflammatory processes that, in turn, impact neuronal Ca2+ 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 Ca2+ homeostasis dysregulation in AD.

Keywords: astrocyte; calcium homeostasis; disease; microglia; neuroinflammation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / pathology
  • Astrocytes / pathology
  • Homeostasis
  • Humans
  • Microglia* / pathology
  • Neuroinflammatory Diseases
  • Plaque, Amyloid

Grants and funding

This research was funded by the PRIN grant no. 2017YH3SXK from the Italian Ministry of Research.