Ting Simon Kang Seng, Benzinger Tammie, Kepe Vladimir, Fagan Anne, Coppola Giovanni, Porter Verna, Hecimovic Silva, Chakraverty Suma, Alvarez-Retuerto Ana Isabel, Goate Alison, Ringman John M
Department of Neurology, Singapore General Hospital, Singapore.
Departments of Radiology and Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA.
J Alzheimers Dis. 2014;40(2):271-5. doi: 10.3233/JAD-131844.
Mutations in PSEN1 are the most common cause of autosomal dominant familial Alzheimer's disease (FAD). We describe an African-American woman with a family history consistent with FAD who began to experience cognitive decline at age 50. Her clinical presentation, MRI, FDG-PET, and PIB-PET scan findings were consistent with AD and she was found to have a novel I238M substitution in PSEN1. As this mutation caused increased production of Aβ42 in an in vitro assay, was not present in two population databases, and is conserved across species, it is likely to be pathogenic for FAD.
早老素1（PSEN1）突变是常染色体显性遗传家族性阿尔茨海默病（FAD）最常见的病因。我们描述了一位非裔美国女性，其家族病史与FAD相符，50岁开始出现认知能力下降。她的临床表现、MRI、FDG-PET和PIB-PET扫描结果均与阿尔茨海默病一致，并且发现她的PSEN1基因有一个新的I238M替换突变。由于该突变在体外试验中导致β淀粉样蛋白42（Aβ42）生成增加，在两个群体数据库中均未出现，且在物种间保守，因此很可能是FAD的致病原因。
