Journal Article

Synergy between amyloid-β and tau in Alzheimer’s disease

Busche, Marc Aurel, Hyman, Bradley T

2020

Overview

Patients with Alzheimer’s disease (AD) present with both extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles in the brain. For many years, the prevailing view of AD pathogenesis has been that changes in Aβ precipitate the disease process and initiate a deleterious cascade involving tau pathology and neurodegeneration. Beyond this ‘triggering’ function, it has been typically presumed that Aβ and tau act independently and in the absence of specific interaction. However, accumulating evidence now suggests otherwise and contends that both pathologies have synergistic effects. This could not only help explain negative results from anti-Aβ clinical trials but also suggest that trials directed solely at tau may need to be reconsidered. Here, drawing from extensive human and disease model data, we highlight the latest evidence base pertaining to the complex Aβ–tau interaction and underscore its crucial importance to elucidating disease pathogenesis and the design of next-generation AD therapeutic trials.Busche and Hyman review emerging evidence for an interaction between Aβ and tau during Alzheimer’s disease (AD) progression that challenges the classical linear trajectory model and offers a new perspective on AD pathophysiology and therapy.

• Publisher: Nature Publishing Group
• Subject: Alzheimer's disease / Clinical trials / Neurodegenerative diseases / Neurofibrillary tangles / Pathogenesis / Pathophysiology / Synergistic effect / Tau protein / β-Amyloid