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阿尔茨海默病的疾病修饰药物。

Disease-modifying drugs in Alzheimer's disease.

作者信息

Ghezzi Laura, Scarpini Elio, Galimberti Daniela

机构信息

Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

Drug Des Devel Ther. 2013 Dec 6;7:1471-8. doi: 10.2147/DDDT.S41431.

Abstract

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques) and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition.

摘要

阿尔茨海默病(AD)是一种与年龄相关的神经退行性疾病,也是痴呆最常见的病因。AD的早期特征是短期记忆丧失。一旦疾病进展,患者会出现方向感、口头交流、计算、学习能力和认知思维方面的困难。该疾病的中位病程为10年。其病理特征是β-淀粉样肽(所谓的老年斑)沉积以及以神经原纤维缠结形式存在的tau蛋白。目前,欧洲药品管理局批准了两类药物用于治疗AD,即用于轻度至中度AD的乙酰胆碱酯酶抑制剂,以及用于中度和重度AD的N-甲基-D-天冬氨酸受体拮抗剂美金刚。使用乙酰胆碱酯酶抑制剂或美金刚进行治疗旨在减缓疾病进展并控制症状,而正在研发的药物则旨在改变导致AD的病理步骤。在此,我们综述了现有乙酰胆碱酯酶抑制剂和美金刚的临床特征、药理特性及成本效益,并重点关注旨在干扰β-淀粉样肽的疾病修饰药物,包括疫苗接种、被动免疫和tau沉积。

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