Hampel, H;
Hardy, J;
Blennow, K;
Chen, C;
Perry, G;
Kim, SH;
Villemagne, VL;
... Vergallo, A; + view all
(2021)
The Amyloid-beta Pathway in Alzheimer's Disease.
Molecular Psychiatry
10.1038/s41380-021-01249-0.
(In press).
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Abstract
Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer’s disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aβ pathway dyshomeostasis in AD pathophysiological dynamics. We discuss the evidence highlighting a differentiated interaction of distinct Aβ species with other AD-related biological mechanisms, such as tau-mediated, neuroimmune and inflammatory changes, as well as a neurochemical imbalance. Through the lens of the latest development of multimodal in vivo biomarkers of AD, this cross-disciplinary review examines the compelling hypothesis- and data-driven rationale for Aβ-targeting therapeutic strategies in development for the early treatment of AD.
| Type: | Article |
|---|---|
| Title: | The Amyloid-beta Pathway in Alzheimer's Disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41380-021-01249-0 |
| Publisher version: | https://doi.org/10.1038/s41380-021-01249-0 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Neurosciences, Psychiatry, Neurosciences & Neurology, BASAL FOREBRAIN ATROPHY, APOLIPOPROTEIN-E GENOTYPE, BLOOD-BRAIN-BARRIER, DENSITY-LIPOPROTEIN RECEPTOR, IMPAIR SYNAPTIC PLASTICITY, GAMMA-SECRETASE ACTIVITY, GENOME-WIDE ASSOCIATION, PRECURSOR PROTEIN GENE, A-BETA, CEREBROSPINAL-FLUID |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10134470 |
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