Modes of Aβ toxicity in Alzheimer’s disease
Open Access
- 25 June 2011
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Life Sciences
- Vol. 68 (20), 3359-3375
- https://doi.org/10.1007/s00018-011-0750-2
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.Keywords
This publication has 196 references indexed in Scilit:
- Longitudinal assessment of Aβ and cognition in aging and Alzheimer diseaseAnnals of Neurology, 2011
- Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE GenotypesArchives of Neurology, 2010
- Transsynaptic Progression of Amyloid-β-Induced Neuronal Dysfunction within the Entorhinal-Hippocampal NetworkNeuron, 2010
- Posttranscriptional Regulation of MicroRNA Biogenesis in AnimalsMolecular Cell, 2010
- Convergence of Amyloid-β and Tau Pathologies on Mitochondria In VivoMolecular Neurobiology, 2010
- Epilepsy and Cognitive Impairments in Alzheimer DiseaseArchives of Neurology, 2009
- Proteomics in animal models of Alzheimer's and Parkinson's diseasesAgeing Research Reviews, 2009
- Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degenerationActa Neuropathologica, 2007
- Synaptic plasticity: one STEP at a timeTrends in Neurosciences, 2006
- Neuropathological stageing of Alzheimer-related changesActa Neuropathologica, 1991