title: Dystrophic neurites in TgCRND8 and Tg2576 mice mimic human pathological brain aging.
abstract: The morphology and neurochemistry of beta-amyloid (A beta) plaque-associated dystrophic neurites present in TgCRND8 and Tg2576 mice was demonstrated to be strikingly similar to that observed in pathologically aged human cases, but not in Alzheimer's disease (AD) cases. Specifically, pathologically aged cases and both transgenic mouse lines exhibited alpha-internexin- and neurofilament-triplet-labelled ring- and bulb-like dystrophic neurites, but no classical hyperphosphorylated-tau dystrophic neurite pathology. In contrast, AD cases demonstrated abundant classical hyperphosphorylated-tau-labelled dystrophic neurites, but no neurofilament-triplet-labelled ring-like dystrophic neurites. Importantly, quantitation demonstrated that the A beta plaques in TgCRND8 mice were highly axonopathic, and localised displacement or clipping of apical dendrite segments was also associated with A beta plaques in both transgenic mouse models. These results suggest that neuronal pathology in these mice represent an accurate and valuable model for understanding, and developing treatments for, the early brain changes of AD.
authors.affiliation: NeuroRepair Group, Menzies Research Institute, 43 Collins Street, Hobart, 7001 Tasmania, Australia. awoodhou@utas.edu.au
authors.forename: Adele
authors.initials: A
authors.lastname: Woodhouse
authors.forename: James C
authors.initials: JC
authors.lastname: Vickers
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.forename: Tracey C
authors.initials: TC
authors.lastname: Dickson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides