Triple-transgenic Alzheimer's disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology

Glia. 2009 Jan 1;57(1):54-65. doi: 10.1002/glia.20734.


Alzheimer's disease (AD) is a progressively debilitating brain disorder pathologically defined by extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and synaptic disintegrity. AD has not been widely considered a disease of white matter, but more recent evidence suggests the existence of abnormalities in myelination patterns and myelin attrition in AD-afflicted human brains. Herein, we demonstrate that triple-transgenic AD (3xTg-AD) mice, which harbor the human amyloid precursor protein Swedish mutant transgene, presenilin knock-in mutation, and tau P301L mutant transgene, exhibit significant region-specific alterations in myelination patterns and in oligodendrocyte marker expression profiles at time points preceding the appearance of amyloid and tau pathology. These immunohistochemical signatures are coincident with age-related alterations in axonal and myelin sheath ultrastructure as visualized by comparative electron microscopic examination of 3xTg-AD and nontransgenic mouse brain tissue. Overall, these findings indicate that 3xTg-AD mice represent a viable model in which to examine mechanisms underlying AD-related myelination and neural transmission defects that occur early during presymptomatic stages of the disease process.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Brain / ultrastructure
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin Sheath / genetics
  • Myelin Sheath / pathology*
  • Myelin Sheath / ultrastructure
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / pathology
  • Nerve Fibers, Myelinated / ultrastructure
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / pathology*
  • Plaque, Amyloid / ultrastructure
  • Tauopathies / genetics
  • Tauopathies / metabolism
  • Tauopathies / pathology*
  • tau Proteins / genetics
  • tau Proteins / metabolism
  • tau Proteins / ultrastructure


  • tau Proteins