de la Torre Jack C
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Lancet Neurol. 2004 Mar;3(3):184-90. doi: 10.1016/S1474-4422(04)00683-0.
The cause of Alzheimer's disease (AD) is unknown. This gap in knowledge has created a stumbling block in the search for a genuinely effective treatment or cure for this dementia. This article summarises the arguments for a causal role for either amyloid deposition or cerebrovascular pathology as the primary trigger in the development of non-genetic AD. A bare-bones survey of the published research reveals no compelling evidence that amyloid deposition is neurotoxic in human beings or that it results in neurodegenerative changes involving synaptic, metabolic, or neuronal loss in human or transgenic-mouse brains. By contrast, the data supporting AD as a primary vascular disorder are more convincing. Findings suggesting a vascular cause of AD come from epidemiological, neuroimaging, pathological, pharmacotherapeutic, and clinical studies. The consensus of these studies indicates that chronic brain hypoperfusion is linked to AD risk factors, AD preclinical detection and pharmacotherapeutic action of AD symptoms.
阿尔茨海默病（AD）的病因尚不清楚。这一知识空白在寻找针对这种痴呆症的真正有效治疗方法或治愈手段的过程中形成了一个绊脚石。本文总结了关于淀粉样蛋白沉积或脑血管病理作为非遗传性AD发病主要触发因素的因果作用的相关论点。对已发表研究的简要调查显示，没有令人信服的证据表明淀粉样蛋白沉积在人类中具有神经毒性，或者它会导致人类或转基因小鼠大脑中涉及突触、代谢或神经元丧失的神经退行性变化。相比之下，支持AD是一种原发性血管疾病的数据更具说服力。表明AD存在血管病因的研究结果来自流行病学、神经影像学、病理学、药物治疗学和临床研究。这些研究的共识表明，慢性脑灌注不足与AD风险因素、AD临床前检测以及AD症状的药物治疗作用有关。
