Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model Academic Article uri icon


MeSH Major

  • Alzheimer Disease
  • Brain
  • Oxidative Stress
  • Plaque, Amyloid
  • Thiamine Deficiency


  • Mitochondrial dysfunction, oxidative stress and reductions in thiamine-dependent enzymes have been implicated in multiple neurological disorders including Alzheimer's disease (AD). Experimental thiamine deficiency (TD) is an established model for reducing the activities of thiamine-dependent enzymes in brain. TD diminishes thiamine-dependent enzymes throughout the brain, but produces a time-dependent selective neuronal loss, glial activation, inflammation, abnormalities in oxidative metabolism and clusters of degenerating neurites in only specific thalamic regions. The present studies tested how TD alters brain pathology in Tg19959 transgenic mice over expressing a double mutant form of the amyloid precursor protein (APP). TD exacerbated amyloid plaque pathology in transgenic mice and enlarged the area occupied by plaques in cortex, hippocampus and thalamus by 50%, 200% and 200%, respectively. TD increased Abeta(1-42) levels by about three fold, beta-CTF (C99) levels by 33% and beta-secretase (BACE1) protein levels by 43%. TD-induced inflammation in areas of plaque formation. Thus, the induction of mild impairment of oxidative metabolism, oxidative stress and inflammation induced by TD alters metabolism of APP and/or Abeta and promotes accumulation of plaques independent of neuron loss or neuritic clusters.

publication date

  • October 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2782730

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2007.12.013

PubMed ID

  • 18406011

Additional Document Info

start page

  • 1587

end page

  • 600


  • 30


  • 10