Laboratory of Physiology, Pharmacology and Psychopathology, Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, Brazil.
Laboratory for research into care, patient safety, and technological innovation in nursing and health, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Basic Clin Pharmacol Toxicol. 2024 May;134(5):563-573. doi: 10.1111/bcpt.13996. Epub 2024 Mar 8.
Dementia is an umbrella term for a broad group of age-associated neurodegenerative diseases. It is estimated that dementia affects 50 million people worldwide and that Alzheimer's disease (AD) is responsible for up to 75% of cases. Small extracellular senile plaques composed of filamentous aggregates of amyloid β (Aβ) protein tend to bind to neuronal receptors, affecting cholinergic, serotonergic, dopaminergic and noradrenergic neurotransmission, leading to neuroinflammation, among other pathophysiologic processes and subsequent neuronal death, followed by dementia. The amyloid cascade hypothesis points to a pathological process in the cleavage of the amyloid precursor protein (APP), resulting in pathological Aβ. There is a close relationship between the pathologies that lead to dementia and depression. It is estimated that depression is prevalent in up to 90% of individuals diagnosed with Parkinson's disease, with varying severity, and in 20 to 30% of cases of Alzheimer's disease. The hypothalamic pituitary adrenal (HPA) axis is the great intermediary between the pathophysiological mechanisms in neurodegenerative diseases and depression. This review discusses the role of Aβ protein in the pathophysiological mechanisms of dementia and depression, considering the HPA axis, neuroinflammation, oxidative stress, signalling pathways and neurotransmission.
痴呆是一组与年龄相关的神经退行性疾病的统称。据估计，全球有 5000 万人患有痴呆症，其中阿尔茨海默病（AD）占病例的 75%左右。由淀粉样β（Aβ）蛋白丝状聚集组成的小细胞外老年斑倾向于与神经元受体结合，影响胆碱能、5-羟色胺能、多巴胺能和去甲肾上腺素能神经传递，导致神经炎症等病理生理过程和随后的神经元死亡，进而导致痴呆。淀粉样蛋白级联假说指出了淀粉样前体蛋白（APP）裂解导致病理性 Aβ的病理过程。导致痴呆和抑郁的病理之间存在密切关系。据估计，高达 90%的帕金森病患者、不同严重程度的患者以及 20%至 30%的阿尔茨海默病患者都患有抑郁症。下丘脑-垂体-肾上腺（HPA）轴是神经退行性疾病的病理生理机制与抑郁之间的主要中介。这篇综述讨论了 Aβ蛋白在痴呆和抑郁的病理生理机制中的作用，同时考虑了 HPA 轴、神经炎症、氧化应激、信号通路和神经传递。
