The dendritic hypothesis for Alzheimer's disease pathophysiology

• Dendritic neuropathology is ubiquitous in Alzheimer's Disease (AD).
• Aβ causes dendritic neuropathology in AD.
• Dendritic mislocalization of Tau is an early feature of AD.
• Tau mediates dendritic dysfunction in AD models.
• Addressing dysfunctional dendritic pathways holds promise for AD treatment.

Converging evidence indicates that processes occurring in and around neuronal dendrites are central to the pathogenesis of Alzheimer's disease. These data support the concept of a “dendritic hypothesis” of AD, closely related to the existing synaptic hypothesis. Here we detail dendritic neuropathology in the disease and examine how Aβ, tau, and AD genetic risk factors affect dendritic structure and function. Finally, we consider potential mechanisms by which these key drivers could affect dendritic integrity and disease progression. These dendritic mechanisms serve as a framework for therapeutic target identification and for efforts to develop disease-modifying therapeutics for Alzheimer's disease.This article is part of a special issue Dendrites and Disease.