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

Data:	2018
Resum:	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
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Llengua:	Anglès
Document:	Article de revisió ; recerca ; Versió acceptada per publicar
Matèria:	Amyloid-β peptide ; Amyloid-β protein precursor ; Oligomers ; Synaptic dysfunction ; Tau
Publicat a:	Journal of Alzheimer's disease, Vol. 64 Núm. s1 (2018) , p. S611-S631, ISSN 1875-8908

DOI: 10.3233/JAD-179935
PMID: 29865055

52 p, 705.6 KB

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