Saggu Shalini, Bai Ava, Aida Mae, Rehman Hasibur, Pless Andrew, Ware Destany, Deak Ferenc, Jiao Kai, Wang Qin
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA.
Center for Biotechnology and Genomic Medicine, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA.
Geroscience. 2025 Feb;47(1):457-482. doi: 10.1007/s11357-024-01359-x. Epub 2024 Sep 27.
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.
阿尔茨海默病(AD)是一种毁灭性的神经退行性疾病,其特征是认知功能持续下降,并出现严重干扰性的神经精神症状。随着疾病的进展,它会呈现出一系列严重的神经精神表现,包括使人衰弱的抑郁、焦虑、激越以及令人痛苦的精神病发作。由血清素、多巴胺和去甲肾上腺素调节的单胺能系统的复杂网络,对我们的情绪、认知和行为有着显著影响。新出现的证据表明,该系统的失调和退化在AD早期就已发生,导致这些关键神经递质的水平、代谢和受体功能出现明显改变。然而,单胺能神经元的退化以及随后的代偿性变化如何导致阿尔茨海默病中观察到的神经精神症状,仍不清楚。这篇综述综合了目前关于AD中单胺变化的研究结果,并探讨了这些变化如何导致该疾病的神经精神症状。通过阐明AD相关精神症状的生物学基础,我们旨在强调其复杂性,并为治疗AD中的神经精神症状提供创新方法。