A Novel PSEN1 Mutation (I238M) associated with Early-Onset Alzheimer's Disease in an African-American Woman

被引：13

作者：

Ting, Simon Kang Seng ^{[1
]}

Benzinger, Tammie ^{[2
,3
]}

Kepe, Vladimir ^{[4
]}

Fagan, Anne ^{[5
]}

Coppola, Giovanni ^{[6
,7
]}

Porter, Verna ^{[6
]}

Hecimovic, Silva ^{[8
]}

Chakraverty, Suma ^{[9
]}

Alvarez-Retuerto, Ana Isabel ^{[6
,7
]}

Goate, Alison ^{[9
]}

Ringman, John M. ^{[6
,7
]}

机构：

[1] Singapore Gen Hosp, Dept Neurol, Singapore, Singapore

[2] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO USA

[4] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[5] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA

[8] Rudjer Boskovic Inst, Dept Mol Med, Zagreb, Croatia

[9] Washington Univ, Dept Psychiat, St Louis, MO USA

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2014年 / 40卷 / 02期

关键词：

African; Alzheimer's disease; amyloid-beta(42); autosomal dominant; familial; gamma-secretase; in vitro; PIB-PET; presenilin-1; PSEN1; PRESENILIN-1; MUTATION; FAMILY; APP; BETA;

D O I：

10.3233/JAD-131844

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 A beta(42) 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.

引用

页码：271 / 275

页数：5

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