临床前家族性阿尔茨海默病患者的脑脊液生物标志物与接近诊断时间的相关性。
Cerebrospinal fluid biomarkers and proximity to diagnosis in preclinical familial Alzheimer's disease.
机构信息
Mary S. Easton Center for Alzheimer's Disease Research at UCLA, Los Angeles, Calif., USA.
出版信息
Dement Geriatr Cogn Disord. 2012;33(1):1-5. doi: 10.1159/000335729. Epub 2012 Feb 13.
BACKGROUND/AIMS: Biological markers of utility in tracking Alzheimer's disease (AD) during the presymptomatic prodromal phase are important for prevention studies. Changes in cerebrospinal fluid (CSF) levels of 42-amino-acid β-amyloid (Aβ(42)), total tau protein (t-tau) and phosphorylated tau at residue 181 (p-tau(181)) during this state are incompletely characterized.
METHODS
We measured CSF markers in 13 carriers of familial AD (FAD) mutations that are fully penetrant for causing AD (PSEN1 and APP) and in 5 non-mutation-carrying family members.
RESULTS
Even among the entirely presymptomatic mutation carriers (n = 9), Aβ(42) was diminished (388.7 vs. 618.4 pg/ml, p = 0.004), and t-tau (138.5 vs. 50.5 pg/ml, p = 0.002) and p-tau(181) (71.7 vs. 24.6 pg/ml, p = 0.003) were elevated. There was a negative correlation between Aβ(42) levels and age relative to the family-specific age of dementia diagnosis.
CONCLUSIONS
Our data are consistent with a decline in CSF Aβ(42) levels occurring at least 20 years prior to clinical dementia in FAD.
背景/目的：在具有阿尔茨海默病（AD）前驱症状的无症状期，生物标志物对于跟踪 AD 非常重要，它可用于预防研究。在此状态下，脑脊液（CSF）中 42 个氨基酸β-淀粉样蛋白（Aβ（42））、总tau 蛋白（t-tau）和磷酸化 tau 第 181 位（p-tau（181））的水平变化尚未完全确定。
方法
我们测量了 13 名携带完全显性 AD 突变（PSEN1 和 APP）的家族性 AD（FAD）突变携带者和 5 名非突变携带者的 CSF 标志物。
结果
即使在完全无症状的突变携带者（n = 9）中，Aβ（42）也减少（388.7 与 618.4 pg/ml，p = 0.004），t-tau（138.5 与 50.5 pg/ml，p = 0.002）和 p-tau（181）（71.7 与 24.6 pg/ml，p = 0.003）升高。Aβ（42）水平与相对于家族特定痴呆诊断年龄的年龄呈负相关。
结论
我们的数据与 FAD 中至少 20 年前发生的 CSF Aβ（42）水平下降一致。
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