Abstract
The monoaminergic nuclei are some of the earliest sites of tau pathology in Alzheimer’s disease (AD), and their dysfunction may help to explain the emergence of common neuropsychiatric and cognitive symptoms.Upregulation of monoaminergic neuromodulator activity early in AD provides evidence for biological mechanisms of resilience to AD pathology and potential for therapeutic intervention.Modern neuroimaging approaches have enabled the precise quantification of the structure and function of monoaminergic nuclei across the course of AD in vivo, demonstrating linkages between monoamine systems and AD pathology in humans.Developments in mobile/wearable technology facilitate the reliable assessment of behavioral changes (e.g., neuropsychiatric symptoms, sleep disturbances, patterns of activity participation) that are associated with early AD pathology and monoamine function.
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.
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.