Roles of microglia in Alzheimer's disease and impact of new findings on microglial heterogeneity as a target for therapeutic intervention

Biochem Pharmacol. 2021 Oct:192:114754. doi: 10.1016/j.bcp.2021.114754. Epub 2021 Sep 1.

Abstract

Microglia are specialized macrophages that reside within the central nervous system and play key roles in brain immunity, development and homeostasis. Recent studies also revealed functions of microglia in neuroprotection and neuroinflammation, leading to the discovery that microglia are involved in several brain pathologies including Alzheimer's disease (AD). However, the beneficial and detrimental actions of this intriguing cell population can be challenging to dissect: the advent of single-cell and single-nucleus transcriptomic technologies has revolutionized our understanding of the heterogeneity of multiple cell types and is now being applied to the study of microglia in health and disease. Here, we review recent findings on microglial biology, focusing on insights from single cell transcriptomic studies and the heterogeneity that they reveal, and consider the impact of these findings on our understanding of AD. We also discuss how microglia might represent a next-generation therapeutic target for treatment of AD and other neuroinflammatory conditions.

Keywords: Alzheimer’s disease; Heterogeneity; Microglia; Neuroinflammation; Neuroprotection; Single cell resolution.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Drug Delivery Systems / methods*
  • Humans
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • Neuroprotective Agents / administration & dosage*

Substances

  • Neuroprotective Agents