Role of Amyloid-β and Tau Proteins in Alzheimer's Disease : Confuting the Amyloid Cascade
Gulisano, W. (Department of Biomedical and Biotechnological Sciences. Section of Physiology. University of Catania)
Maugeri, Daniele (Department of Biomedical and Biotechnological Sciences. Section of Physiology. University of Catania)
Baltrons Soler, Ma. Antonia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Fà, Mauro (Taub Institute for Research on Alzheimer's Disease and the Aging Brain. Department of Medicine. Columbia University)
Amato, Arianna (Department of Anaesthesiology. Università Cattolica Del Sacro Cuore)
Palmeri, Agostino (Department of Biomedical and Biotechnological Sciences. Section of Physiology. University of Catania)
D'Adamio, Luciano (Rutgers University. Department of Pharmacology. Physiology and Neuroscience)
Grassi, Claudio (Institute of Human Physiology. Università Cattolica Del Sacro Cuore)
Devanand, D.P. (Department of Psychiatry. Columbia University. College of Phys. and Surg.)
Honig, Lawrence S. (Department of Neurology. Columbia University. College of Phys. and Surg.)
Puzzo, Daniela (University of Catania. Department of Biomedical and Biotechnological Sciences)
Arancio, Ottavio (Taub Institute for Research on Alzheimer's Disease and the Aging Brain. Department of Medicine. Columbia University)

Fecha:	2018
Resumen:	The "Amyloid Cascade Hypothesis" has dominated the Alzheimer's disease (AD) field in the last 25 years. It posits that the increase of amyloid-β (Aβ) is the key event in AD that triggers tau pathology followed by neuronal death and eventually, the disease. However, therapeutic approaches aimed at decreasing Aβ levels have so far failed, and tau-based clinical trials have not yet produced positive findings. This begs the question of whether the hypothesis is correct. Here we have examined literature on the role of Aβ and tau in synaptic dysfunction, memory loss, and seeding and spreading of AD, highlighting important parallelisms between the two proteins in all of these phenomena. We discuss novel findings showing binding of both Aβ and tau oligomers to amyloid-β protein precursor (AβPP), and the requirement for the presence of this protein for both Aβ and tau to enter neurons and induce abnormal synaptic function and memory. Most importantly, we propose a novel view of AD pathogenesis in which extracellular oligomers of Aβ and tau act in parallel and upstream of AβPP. Such a view will call for a reconsideration of therapeutic approaches directed against Aβ and tau, paving the way to an increased interest toward AβPP, both for understanding the pathogenesis of the disease and elaborating new therapeutic strategies.
Nota:	Altres ajuts: R01 AG017761/AG/NIA NIH HHS/United States; R01 AG049402/AG/NIA NIH HHS/United States
Derechos:	Tots els drets reservats.
Lengua:	Anglès
Documento:	Ressenya ; recerca ; Versió acceptada per publicar
Materia:	Amyloid-β peptide ; Amyloid-β protein precursor ; Oligomers ; Synaptic dysfunction ; Tau
Publicado en:	Journal of Alzheimer's disease, Vol. 64 Núm. s1 (2018) , p. S611-S631, ISSN 1875-8908

DOI: 10.3233/JAD-179935
PMID: 29865055

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