title: Modes of Aβ toxicity in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide.
authors.affiliation: Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia. juergen.goetz@sydney.edu.au
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
authors.forename: Anne
authors.initials: A
authors.lastname: Eckert
authors.forename: Miriam
authors.initials: M
authors.lastname: Matamales
authors.forename: Lars M
authors.initials: LM
authors.lastname: Ittner
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice
chemical_list: D016229:Amyloid beta-Peptides