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https://doi.org/10.1038/s41380-021-01249-0
Title: | The Amyloid-beta Pathway in Alzheimer's Disease | Authors: | Hampel, Harald Hardy, John Blennow, Kaj Chen, Christopher Perry, George Kim, Seung Hyun Villemagne, Victor L Aisen, Paul Vendruscolo, Michele Iwatsubo, Takeshi Masters, Colin L Cho, Min Lannfelt, Lars Cummings, Jeffrey L Vergallo, Andrea |
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 |
Issue Date: | 30-Aug-2021 | Publisher: | SPRINGERNATURE | Citation: | Hampel, Harald, Hardy, John, Blennow, Kaj, Chen, Christopher, Perry, George, Kim, Seung Hyun, Villemagne, Victor L, Aisen, Paul, Vendruscolo, Michele, Iwatsubo, Takeshi, Masters, Colin L, Cho, Min, Lannfelt, Lars, Cummings, Jeffrey L, Vergallo, Andrea (2021-08-30). The Amyloid-beta Pathway in Alzheimer's Disease. MOLECULAR PSYCHIATRY 26 (10) : 5481-5503. ScholarBank@NUS Repository. https://doi.org/10.1038/s41380-021-01249-0 | 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. | Source Title: | MOLECULAR PSYCHIATRY | URI: | https://scholarbank.nus.edu.sg/handle/10635/218739 | ISSN: | 1359-4184 1476-5578 |
DOI: | 10.1038/s41380-021-01249-0 |
Appears in Collections: | Staff Publications Elements |
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The Amyloid-β Pathway in Alzheimers Disease.pdf | 2.43 MB | Adobe PDF | OPEN | None | View/Download |
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