title: Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice.
abstract: Alzheimer's disease (AD) is a neurodegenerative disease hallmarked by extracellular Aβ(1-42) containing plaques, and intracellular neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Progressively, memory deficits and cognitive disabilities start to occur as these hallmarks affect hippocampus and frontal cortex, regions highly involved in memory. Connective tissue growth factor (CTGF) expression, which is high in the vicinity of Aβ plaques and NFTs, was found to influence γ-secretase activity, the molecular crux in Aβ(1-42) production. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that downregulates CTGF expression in hepatocytes and has been shown to possess therapeutic efficacy in neurodegenerative models. To investigate the possible in vivo therapeutic effects of TUDCA, we provided 0.4% TUDCA-supplemented food to APP/PS1 mice, a well-established AD mouse model. Six months of TUDCA supplementation prevented the spatial, recognition and contextual memory defects observed in APP/PS1 mice at 8 months of age. Furthermore, TUDCA-supplemented APP/PS1 mice displayed reduced hippocampal and prefrontal amyloid deposition. These effects of TUDCA supplementation suggest a novel mechanistic route for Alzheimer therapeutics.
authors.affiliation: Laboratory of Biological Psychology, Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Lo
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Callaerts-Vegh
authors.forename: Ana F
authors.initials: AF
authors.lastname: Nunes
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
authors.forename: Rudi
authors.initials: R
authors.lastname: D'Hooge
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D058227:Amyloidogenic Proteins / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D003072:Cognition Disorders / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D058227:Amyloidogenic Proteins; D002756:Cholagogues and Choleretics; D053764:Presenilin-1; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine