伴痉挛性截瘫的早发阿尔茨海默病的一种新的早老素-1突变(Leu 85 Pro)

作     者：Ataka S. Tomiyama T. Takuma H. H.Mori 王英鹏 

作者机构：Department of Neuroscience Osaka City University Medical Schoo l 1-4-3 Asahimachi Abenoku Osaka 545-8585 Japan Dr. 

出 版 物：《世界核心医学期刊文摘（神经病学分册）》 (Digest of the World Core Medical Journals:Clinical Neurology)

年 卷 期：2005年第1卷第3期

页      面：25-26页

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

主　　题：痉挛性截瘫 Leu 85 Pro 阿尔茨海默病 淀粉样前体蛋白 基因突变 表型差异 变异型 基因转染 突变型 基因序列 

摘      要：Background: Early onset familial Alzheimer disease is caused by mutations in the amyloid precursor protein (APP), prese nilin 1 (PSEN1), or presenilin 2 ( PSEN2) genes. Phenotypic diversity has been reported to be associated with vario us mutations in PSEN1. Various mutations of PSEN1 have been reported in cases of early onset Alzheimer disease with spastic paraparesis. Objective: To describe a novel mutation in the PSEN1 gene associated with early onset Alzheimer disea se with spastic paraparesis. Patient and Methods: The patient was a 27 year ol d man who developed early onset dementia with spastic paraparesis. We examined sequences of the PSEN1, PSEN2, and APP genes from the patient and his family. To detect a possible mutation effect on the production of amyloid β.peptide (Aβ ), transfected HEK293 cells were examined for Aβ42 and Aβ40 production. Result s: We found a novel mutation (Leu85Pro) in PSEN1. This mutation influenced the p roduction of Aβ, resulting in a 2 fold elevation of Aβ42 production and of th e Aβ42/40 ratio. Conclusion: To our knowledge, this is the first report of very early onset Alzheimer disease with spastic paraparesis and with the visual var iant form of the disease, which is associated with visuospatial cognitive disord er. The Leu85Pro mutation in PSEN1 was pathogenic.