Monoamine alterations in Alzheimer’s disease and their implications in comorbid neuropsychiatric symptoms

Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by relentless cognitive decline and the emergence of profoundly disruptive neuropsychiatric symptoms. As the disease progresses, it unveils a formidable array of neuropsychiatric manifestations, including debilitating depression, anxiety, agitation, and distressing episodes of psychosis. The intricate web of the monoaminergic system, governed by serotonin, dopamine, and norepinephrine, significantly influences our mood, cognition, and behavior. Emerging evidence suggests that dysregulation and degeneration of this system occur early in AD, leading to notable alterations in these critical neurotransmitters’ levels, metabolism, and receptor function. However, how the degeneration of monoaminergic neurons and subsequent compensatory changes contribute to the presentation of neuropsychiatric symptoms observed in Alzheimer’s disease remains elusive. This review synthesizes current findings on monoamine alterations in AD and explores how these changes contribute to the neuropsychiatric symptomatology of the disease. By elucidating the biological underpinnings of AD-related psychiatric symptoms, we aim to underscore the complexity and inform innovative approaches for treating neuropsychiatric symptoms in AD. Graphical Abstract [created With Biorender.com]

Bibliographic Information