Document Type

Article

Publication Date

8-30-2021

Publication Title

Molecular Psychiatry

First page number:

1

Last page number:

23

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.

Keywords

Diagnostic markers; Disease; Neuroscience

Disciplines

Cognitive Neuroscience | Molecular and Cellular Neuroscience

File Format

pdf

File Size

2400 KB

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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