Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the elderly globally. Emerging evidence has demonstrated microglia-driven neuroinflammation as a key contributor to the onset and progression of AD, however, the mechanisms that mediate neuroinflammation remain largely unknown. Recent studies have suggested mitochondrial dysfunction including mitochondrial DNA (mtDNA) damage, metabolic defects, and quality control (QC) disorders precedes microglial activation and subsequent neuroinflammation. Therefore, an in-depth understanding of the relationship between mitochondrial dysfunction and microglial activation in AD is important to unveil the pathogenesis of AD and develop effective approaches for early AD diagnosis and treatment.

• 1
  mtDNA abnormality triggers mitochondrial dysfunction, causing inflammatory responses and microglial activation and ultimately leading to irreversible neuronal death and loss of glial function.
• 2
  Microglial mitochondrial energy metabolism disorder and metabolic reprogramming have been reported to be directly linked with the pathogenesis of AD.
• 3
  Growing literatures have demonstrated damaged mitochondria in activated microglia due to dysregulation of mitochondrial dynamics in a mouse model of AD.