title: Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model.
abstract: 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.
authors.affiliation: Department of Neurology and Neurosciences, Weill Medical College of Cornell University, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA.
authors.forename: Saravanan S
authors.initials: SS
authors.lastname: Karuppagounder
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Qingli
authors.initials: Q
authors.lastname: Shi
authors.forename: Lian H
authors.initials: LH
authors.lastname: Chen
authors.forename: Steve
authors.initials: S
authors.lastname: Pedrini
authors.forename: David
authors.initials: D
authors.lastname: Pechman
authors.forename: Harriet
authors.initials: H
authors.lastname: Baker
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Sam E
authors.initials: SE
authors.lastname: Gandy
authors.forename: Gary E
authors.initials: GE
authors.lastname: Gibson
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009457:Neuroglia / Q000276:immunology / Q000473:pathology / Q000502:physiology; D015213:Neuroimmunomodulation / Q000502:physiology; D009474:Neurons / Q000276:immunology / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology / Q000502:physiology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics; D013832:Thiamine Deficiency / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse