The genetics of very early onset Alzheimer disease
The genetics of very early onset Alzheimer disease
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DOI：
10.1097/wnn.0b013e318145a8c8
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发表时间：
2007-09-01
影响因子：
1.4
通讯作者：
Ghetti, Bernarno
中科院分区：
文献类型：
--
作者：
Filley, Christopher M.;Rollins, Yvonne D.;Ghetti, Bernarno
目的：本研究旨在阐明极早发性阿尔茨海默病(VEOAD)的遗传学，该疾病定义为35岁之前开始的AD。背景：早发性AD(EOAD)是指在65岁之前出现症状，患者可能存在早老素1(PSEN1)、早老素2(PSEN2)或淀粉样前体蛋白突变。VEOAD非常罕见，PSEN1突变也有牵连。我们遇到了一位32岁起患有表型额颞叶痴呆的男性，尸检发现他有常染色体显性痴呆的家族史。方法：对患者的大脑进行组织学和遗传学分析，并对所有已发表的VEOAD病例进行回顾。结果：组织学结果诊断为晚期AD。对脑组织的遗传评估发现了一个内含子PSEN1多态；没有发现已知的致病突变。文献回顾(1934-2007)共发现101例VEOAD，发病年龄最小为24岁。在所有有明确基因分析的病例中，要么发现了PSEN1突变，要么发现了与14号染色体的连锁。结论：VEOAD可以呈现非典型的临床特征，包括提示额颞部痴呆的发现。所有报告的VEOAD病例经基因分析得出结论，似乎都与PSEN1突变有关。对35岁以下患有痴呆症的成年人进行基因测试可以识别基因缺陷，并帮助诊断和家庭咨询。
Objective: This study was undertaken to clarify the genetics of very early onset Alzheimer disease (VEOAD), defined as AD beginning before age 35.Background: Early onset AD (EOAD) is defined by onset of symptoms before age 65, and affected individuals may harbor a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein. VEOAD is exceedingly rare, and PSEN1 mutations have been implicated. We encountered a man with phenotypic frontotemporal dementia beginning at age 32 and a strong family history Of an autosomal dominant dementia who was found at autopsy to have AD.Methods: Histologic and genetic analyses of the patient's brain were undertaken, and a review of all published VEOAD cases was performed.Results: Histologic findings were diagnostic of advanced stage AD. Genetic evaluation of brain tissue identified an intronic PSEN1 polymorphism; no known pathogenic mutation was found. Literature review (1934 to 2007) disclosed 101 cases of VEOAD; the youngest age of dementia onset was 24 years. In all cases in which definitive genetic analysis was available, either a PSEN1 mutation or linkage to chromosome 14 was found.Conclusions: VEOAD can present with atypical clinical features, including findings suggestive of frontotemporal dementia. All reported cases of VEOAD with conclusive genetic analysis seem to be associated with PSEN1 mutations. Genetic testing in adults younger than 35 with dementia can identify the genetic defect and assist in diagnosis and family counseling.