症状前家族性阿尔茨海默病突变携带者脑脊液中与构象相关的寡聚体。
Conformation-dependent oligomers in cerebrospinal fluid of presymptomatic familial Alzheimer's disease mutation carriers.
作者信息
Ringman John M, Tomic Jennifer L, Coppola Giovanni, Elashoff David, Gylys Karen H, Glabe Charles G
机构信息
Mary S. Easton Center for Alzheimer's Disease Research at UCLA, Calif., USA.
出版信息
Dement Geriatr Cogn Dis Extra. 2012 Jan;2(1):652-7. doi: 10.1159/000345771. Epub 2012 Dec 15.
BACKGROUND/AIMS: Oligomerization of amyloid beta (Aβ) is a hypothesized step in the formation of plaques in Alzheimer's disease (AD) but has been difficult to demonstrate in vivo in humans. As persons destined to develop familial AD (FAD) due to fully penetrant autosomal dominant mutations are essentially certain to develop the disease, they provide the opportunity to identify oligomers during the presymptomatic stage of the disease.
METHODS
We measured levels of Aβ(42) using a conventional immunoassay and prefibrillar, fibrillar, and annular protofibrillar oligomers using polyclonal conformation-dependent antibodies in the cerebrospinal fluid (CSF) of 7 persons at risk for inheriting FAD mutations. Levels of oligomers were compared between FAD mutation carriers and noncarriers.
RESULTS
Compared to 2 noncarriers, annular protofibrillar oligomers were elevated, prefibrillar and fibrillar oligomers trended towards elevation and Aβ(42) monomer trended towards being decreased in 5 FAD mutation carriers.
CONCLUSION
Our data provide evidence for an identifiable elevation of CSF oligomers during the presymptomatic phase of FAD.
背景/目的：淀粉样β蛋白（Aβ）寡聚化被认为是阿尔茨海默病（AD）中斑块形成的一个步骤，但在人体体内很难得到证实。由于因完全显性的常染色体显性突变而注定会患家族性AD（FAD）的人基本上肯定会发病，他们为在疾病的症状前阶段识别寡聚体提供了机会。
方法
我们使用传统免疫分析法测量了7名有遗传FAD突变风险者脑脊液（CSF）中Aβ(42)的水平，并使用多克隆构象依赖性抗体测量了前纤维状、纤维状和环状原纤维寡聚体的水平。比较了FAD突变携带者和非携带者之间寡聚体的水平。
结果
与2名非携带者相比，5名FAD突变携带者中环状原纤维寡聚体水平升高，前纤维状和纤维状寡聚体有升高趋势，Aβ(42)单体有降低趋势。
结论
我们的数据为FAD症状前阶段CSF寡聚体水平可识别的升高提供了证据。
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