1. Models of β-amyloid induced Tau-pathology: the long and 'folded' road to understand the mechanism
- Author
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Ilse Dewachter, Ilie-Cosmin Stancu, Bruno Barbosa de Vasconcelos, and Dick Terwel
- Subjects
Amyloid ,Synaptic dysfunction ,Tau pathology ,Clinical Neurology ,tau Proteins ,Disease ,Review ,Biology ,Cellular and Molecular Neuroscience ,Amyloid cascade hypothesis ,β amyloid ,Alzheimer Disease ,medicine ,Animals ,Humans ,In patient ,Molecular Biology ,Inflammation ,Amyloid beta-Peptides ,Mechanism (biology) ,Alzheimer's disease ,medicine.disease ,3. Good health ,Animal models ,Prion ,Neurology (clinical) ,Amyloid cascade ,Tau ,Neuroscience ,Alzheimer’s disease - Abstract
The amyloid cascade hypothesis has been the prevailing hypothesis in Alzheimer's Disease research, although the final and most wanted proof i.e. fully successful anti-amyloid clinical trials in patients, is still lacking. This may require a better in depth understanding of the cascade. Particularly, the exact toxic forms of Aβ and Tau, the molecular link between them and their respective contributions to the disease process need to be identified in detail. Although the lack of final proof has raised substantial criticism on the hypothesis per se, accumulating experimental evidence in in vitro models, in vivo models and from biomarkers analysis in patients supports the amyloid cascade and particularly Aβ-induced Tau-pathology, which is the focus of this review. We here discuss available models that recapitulate Aβ-induced Tau-pathology and review some potential underlying mechanisms. The availability and diversity of these models that mimic the amyloid cascade partially or more complete, provide tools to study remaining questions, which are crucial for development of therapeutic strategies for Alzheimer's Disease. We thank the Belgian Fonds National pour la Recherche Scientifique –Fonds de la Recherche Scientifique (FNRS-FRS; Qualified Researcher, Impulse Financing, Research Credits), the Institute for the Promotion of Innovation by Science and Technology (IWT) (Belgium), the European Commission (AgedBrainSYSBIO, FP7, ECGA No305299) and the Interuniversity Attraction Poles Programme-Belgian State-Belgian Science Policy, The Belgian Fonds de la Recherche Scientifique Médicale, for financial support. We thank F. Van Leuven for his contribution to this review.
- Published
- 2014