Fessel W J
1 University of California, San Francisco, CA, USA.
2 Kaiser Permanente Medical Care Program, San Francisco, CA, USA.
Am J Alzheimers Dis Other Demen. 2017 May;32(3):166-181. doi: 10.1177/1533317517698790. Epub 2017 Mar 17.
The pathogenesis of Alzheimer's disease involves multiple pathways that, at the macrolevel, include decreased proliferation plus increased loss affecting neurons, astrocytes, and capillaries and, at the subcellular level, involve several elements: amyloid/amyloid precursor protein, presenilins, the unfolded protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented show the intimate, anatomical interactions between neurons, astrocytes, and capillaries; the interactions between the several subcellular factors affecting those cells; and the treatments that are currently available and that might correct dysfunctions in the subcellular factors. Available treatments include lithium, valproate, pioglitazone, erythropoietin, and prazosin. Since the subcellular pathogenesis involves multiple interacting elements, combination treatment would be more effective than administration of a single drug directed at only 1 element. The overall purpose of this presentation is to describe the pathogenesis in detail and to explain the proposed treatments.
阿尔茨海默病的发病机制涉及多个途径，在宏观层面上，包括神经元、星形胶质细胞和毛细血管的增殖减少以及损失增加，在亚细胞层面上，涉及多个因素：淀粉样蛋白/淀粉样前体蛋白、早老素、未折叠蛋白反应、泛素/蛋白酶体系统、Wnt/连环蛋白系统、Notch信号系统、线粒体、线粒体自噬、钙和tau蛋白。所呈现的数据显示了神经元、星形胶质细胞和毛细血管之间密切的解剖学相互作用；影响这些细胞的几个亚细胞因子之间的相互作用；以及目前可用的治疗方法，这些方法可能纠正亚细胞因子中的功能障碍。可用的治疗方法包括锂盐、丙戊酸盐、吡格列酮、促红细胞生成素和哌唑嗪。由于亚细胞发病机制涉及多个相互作用的因素，联合治疗比仅针对一个因素的单一药物给药更有效。本报告的总体目的是详细描述发病机制并解释所提议的治疗方法。
