title: Chronic administration of Dimebon does not ameliorate amyloid-β pathology in 5xFAD transgenic mice.
abstract: Dimebon has been tested as a potential modifier of Alzheimer's disease (AD), resulting in mixed clinical trial outcomes. Originally utilized as an antihistamine, Dimebon was later found to ameliorate AD symptoms in initial human trials. Although subsequent trials have reportedly failed to replicate these finding, there is a growing body of evidence that Dimebon might be neuroprotective in certain models of neurodegeneration. The precise mechanism by which Dimebon is thought to act in AD is unclear, though changes in receptor activity, mitochondria function, and autophagy activity have been proposed. It is thus necessary to test Dimebon in transgenic animal model systems to determine if and how the drug affects development and manifestation of pathology, and which pathogenic processes are altered. In the present study we treated mice harboring five familial mutations associated with hereditary AD (5xFAD line) with a chronic regime of Dimebon. The compound was not found to improve the general health or motor behavior of these mice, nor prevent accumulation of Aβ peptides in the brain. Modest changes in response to an anxiogenic task were, however, detected, suggesting Dimebon might improve behavioral abnormalities and cognition in disease in a mechanism independent of protecting against amyloidosis.
authors: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, United Kingdom.
authors: Owen M
authors: OM
authors: Peters
authors: Tatyana
authors: T
authors: Shelkovnikova
authors: Tatiana
authors: T
authors: Tarasova
authors: Signe
authors: S
authors: Springe
authors: Michail S
authors: MS
authors: Kukharsky
authors: Gaynor A
authors: GA
authors: Smith
authors: Simon
authors: S
authors: Brooks
authors: Sergey A
authors: SA
authors: Kozin
authors: Yury
authors: Y
authors: Kotelevtsev
authors: Sergey O
authors: SO
authors: Bachurin
authors: Natalia
authors: N
authors: Ninkina
authors: Vladimir L
authors: VL
authors: Buchman
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007211:Indoles / Q000008:administration & dosage*; D007858:Learning / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045442:Rotarod Performance Test
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007211:Indoles; C010119:latrepirdine