Role of Amyloid-β and Tau Proteins in Alzheimer's Disease: Confuting the Amyloid Cascade
| Autor: | Devangere P. Devanand, A. Amato, Luciano D'Adamio, Ottavio Arancio, Walter Gulisano, Mauro Fa, Lawrence S. Honig, Marian A Baltrons, Agostino Palmeri, Daniela Puzzo, Daniele Maugeri, Claudio Grassi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tau pathology Amyloid β Settore BIO/09 - FISIOLOGIA tau Proteins Disease Biology Article Pathogenesis 03 medical and health sciences 0302 clinical medicine Alzheimer Disease mental disorders Animals Humans tau oligomers Protein precursor Amyloid-β peptide Amyloid beta-Peptides Neuroscience (all) synaptic dysfunction General Neuroscience General Medicine amyloid-β protein precursor Amyloid β peptide Psychiatry and Mental health Clinical Psychology Synaptic function 030104 developmental biology Geriatrics and Gerontology Amyloid cascade Psychiatry and Mental Health Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | J Alzheimers Dis |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|