Morgese Maria Grazia, Trabace Luigia
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Front Pharmacol. 2019 May 17;10:483. doi: 10.3389/fphar.2019.00483. eCollection 2019.
The prevalence of depression has dramatically increased, and it has been estimated that over 300 million people suffer from depression all over the world. Depression is highly comorbid with many central and peripheral disorders. In this regard, depressive states have been associated with the development of neurological disorders such as Alzheimer's disease (AD). Accordingly, depression is a risk factor for AD and depressive symptomatology is common in pre-clinical AD, representing an early manifestation of this disease. Neuropsychiatric symptoms may represent prodromal symptoms of dementia deriving from neurobiological changes in specific cerebral regions; thus, the search for common biological substrates is becoming an imperative and intriguing field of research. Soluble forms of beta amyloid peptide (Aβ) have been implicated both in the development of early memory deficits and neuropsychiatric symptoms. Indeed, soluble Aβ species have been shown to induce a depressive-like phenotype in AD animal models. Alterations in monoamine content are a common feature of these neuropathologies. Interestingly, serotonergic system modulation has been implicated in alteration of Aβ production. In addition, noradrenaline is considered crucially involved in compensatory mechanisms, leading to increased Aβ degradation several mechanisms, including microglia modulation. In further agreement, antidepressant drugs have also been shown to potentially modulate cognitive symptoms in AD and depression. Thus, the present review summarizes the main knowledge about biological and pathological substrates, such as monoamine and related molecules, commonly involved in AD and depression pathology, thus shading light on new therapeutic approaches.
抑郁症的患病率急剧上升，据估计全球有超过3亿人患有抑郁症。抑郁症与许多中枢和外周疾病高度共病。在这方面，抑郁状态与神经退行性疾病如阿尔茨海默病（AD）的发生有关。因此，抑郁症是AD的一个危险因素，抑郁症状在临床前AD中很常见，是这种疾病的早期表现。神经精神症状可能代表特定脑区神经生物学变化导致的痴呆前驱症状；因此，寻找共同的生物学底物正成为一个紧迫且引人入胜的研究领域。β淀粉样肽（Aβ）的可溶性形式与早期记忆缺陷和神经精神症状的发生都有关。事实上，可溶性Aβ已被证明在AD动物模型中诱导出抑郁样表型。单胺含量的改变是这些神经病理学的一个共同特征。有趣的是，血清素能系统调节与Aβ产生的改变有关。此外，去甲肾上腺素被认为在补偿机制中起关键作用，导致Aβ降解增加，这涉及多种机制，包括小胶质细胞调节。进一步一致的是，抗抑郁药物也已被证明可能调节AD和抑郁症中的认知症状。因此，本综述总结了关于生物和病理底物的主要知识，如单胺和相关分子，它们通常参与AD和抑郁症的病理过程，从而为新的治疗方法提供了线索。
