Short-Term Effects of Microglia-Specific Mitochondrial Dysfunction on Amyloidosis in Transgenic Models of Alzheimer's Disease

J Alzheimers Dis. 2018;65(2):465-474. doi: 10.3233/JAD-180395.


Reduction of mitochondrial activity is a subtle and early event in the pathogenesis of Alzheimer's disease. Mitochondrial damage and consequentially enhanced production of reactive oxygen species is particularly occurring in the vicinity of amyloid plaques. Since all cells are affected by mitochondrial damage, analyses of cell type-specific effects are challenging. To study the impact of mitochondrial alterations on microglial activity in a homogeneous genetic background, we generated bone marrow chimeras of irradiated 46-days-old APP-transgenic mice. For reconstitution, bone marrow from CX3CR1-eGFP mice with mitochondria of either non-obese diabetic or C57BL/6J animals was utilized. Successful reconstitution was evident in 100-day-old animals, by the presence of eGFP-positive cells in liver and spleen. In the brain, one-third of IBA1-positive microglia cells were newly recruited eGFP-expressing cells. Although donor-derived microglia were equally located in the proximity of amyloid plaques, no difference was observed in either the amyloid level, total number, or microglial coverage of plaques. These results indicate that during this brief and early phase of amyloid deposition, beneficial mitochondrial alterations in the newly recruited third of microglial cells were not sufficient to affect the amyloidosis in APP-transgenic mice.

Keywords: Alzheimer’s disease; CX3CR1; amyloid-β; bone marrow cells; microglia; neurodegenerative diseases; neuropathology; rodent models; spleen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Amyloidosis / metabolism*
  • Amyloidosis / pathology
  • Animals
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism
  • Calcium-Binding Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Microfilament Proteins / metabolism
  • Microglia / metabolism*
  • Microglia / pathology
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Diseases / metabolism*
  • Mitochondrial Diseases / pathology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism


  • APP protein, human
  • Aif1 protein, mouse
  • Amyloid beta-Protein Precursor
  • CX3C Chemokine Receptor 1
  • Calcium-Binding Proteins
  • Cx3cr1 protein, mouse
  • Microfilament Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins