Auld Daniel S, Kornecook Tom J, Bastianetto Stéphane, Quirion Rémi
Douglas Hospital Research Centre, 6875 Blvd Lasalle, Verdun, Que, Canada H4H 1R3.
Prog Neurobiol. 2002 Oct;68(3):209-45. doi: 10.1016/s0301-0082(02)00079-5.
Alzheimer's disease (AD) is the most common form of degenerative dementia and is characterized by progressive impairment in cognitive function during mid- to late-adult life. Brains from AD patients show several distinct neuropathological features, including extracellular beta-amyloid-containing plaques, intracellular neurofibrillary tangles composed of abnormally phosphorylated tau, and degeneration of cholinergic neurons of the basal forebrain. In this review, we will present evidence implicating involvement of the basal forebrain cholinergic system in AD pathogenesis and its accompanying cognitive deficits. We will initially discuss recent results indicating a link between cholinergic mechanisms and the pathogenic events that characterize AD, notably amyloid-beta peptides. Following this, animal models of dementia will be discussed in light of the relationship between basal forebrain cholinergic hypofunction and cognitive impairments in AD. Finally, past, present, and future treatment strategies aimed at alleviating the cognitive symptomatology of AD by improving basal forebrain cholinergic function will be addressed.
阿尔茨海默病（AD）是最常见的退行性痴呆形式，其特征是成年中后期认知功能逐渐受损。AD患者的大脑表现出几种不同的神经病理学特征，包括含有细胞外β-淀粉样蛋白的斑块、由异常磷酸化的tau组成的细胞内神经原纤维缠结，以及基底前脑胆碱能神经元的退化。在这篇综述中，我们将提供证据表明基底前脑胆碱能系统参与了AD的发病机制及其伴随的认知缺陷。我们首先将讨论最近的结果，这些结果表明胆碱能机制与表征AD的致病事件之间存在联系，特别是淀粉样β肽。在此之后，将根据基底前脑胆碱能功能减退与AD认知障碍之间的关系来讨论痴呆的动物模型。最后，将探讨过去、现在和未来旨在通过改善基底前脑胆碱能功能来减轻AD认知症状的治疗策略。
