Glia-driven neuroinflammation and systemic inflammation in alzheimer’s disease

Sadayuki Hashioka, Zhou Wu, Andis Klegeris

Research output: Contribution to journalReview articlepeer-review

25 Citations (Scopus)


The neuroinflammatory hypothesis of Alzheimer’s disease (AD) was proposed more than 30 years ago. The involvement of the two main types of glial cells microglia and astrocytes, in neuroinflammation, was suggested early on. In this review, we highlight that the exact contributions of reactive glia to AD pathogenesis remain difficult to define, likely due to the heterogeneity of glia populations and alterations in their activation states through the stages of AD progression. In the case of microglia, it is becoming apparent that both beneficially and adversely activated cell populations can be identified at various stages of AD, which could be selectively targeted to either limit their damaging actions or enhance beneficial functions. In the case of astrocytes, less information is available about potential subpopulations of reactive cells; it also remains elusive whether astrocytes contribute to the neuropathology of AD by mainly gaining neurotoxic functions or losing their ability to support neurons due to astrocyte damage. We identify L-type calcium channel blocker, nimodipine, as a candidate drug for AD, which potentially targets both astrocytes and microglia. It has already shown consistent beneficial effects in basic experimental and clinical studies. We also highlight the recent evidence linking peripheral inflammation and neuroinflammation. Several chronic systemic inflammatory diseases, such as obesity, type 2 diabetes mellitus, and periodontitis, can cause immune priming or adverse activation of glia, thus exacerbating neuroinflammation and increasing risk or facilitating the progression of AD. Therefore, reducing peripheral inflammation is a potentially effective strategy for lowering AD prevalence.

Original languageEnglish
Pages (from-to)908-924
Number of pages17
JournalCurrent Neuropharmacology
Issue number7
Publication statusPublished - Jul 2021

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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