Examining resilience to Alzheimer's disease through the lens of monoaminergic neuromodulator systems.

Abstract

The monoaminergic nuclei are thought to be some of the earliest sites of Alzheimer's disease (AD) pathology in the brain, with tau-containing pretangles appearing in these nuclei decades before the onset of clinical impairments. It has increasingly been recognized that monoamine systems represent a critical target of investigation towards understanding the progression of AD and designing early detection and treatment approaches. This review synthesizes evidence across animal studies, human neuropathology, and state-of-the-art neuroimaging and daily life assessment methods in humans, which demonstrate robust relationships between monoamine systems and AD pathophysiology and behavior. Further, the review highlights the promise of multimethod, multisystem approaches to studying monoaminergic mechanisms of resilience to AD pathology.