Rapid Progression from Mild Cognitive Impairment to Alzheimer's Disease in Subjects with Elevated Levels of Tau in Cerebrospinal Fluid and the APOE ε4/ε4 Genotype
Rapid Progression from Mild Cognitive Impairment to Alzheimer's Disease in Subjects with Elevated Levels of Tau in Cerebrospinal Fluid and the APOE ε4/ε4 Genotype
复制标题
DOI：
10.1159/000216841
复制
发表时间：
2009-01-01
影响因子：
2.4
通讯作者：
Ingelsson, Martin
中科院分区：
文献类型：
--
作者：
Blom, Elin S.;Giedraitis, Vilmantas;Ingelsson, Martin
背景/目的：脑脊液 (CSF) tau 蛋白增加、CSF 淀粉样蛋白-β 42 (A beta 42) 和载脂蛋白 E 基因 (APOE) epsilon 4 等位基因减少可预测从轻度认知障碍 (MCI) 进展为阿尔茨海默病 (AD)。在这里，我们研究了这些标志物，以评估它们的预测价值和对疾病进展率的影响。方法：使用 ELISA，我们测量了 47 名 AD 患者、58 名 MCI 患者和 35 名健康对照受试者的脑脊液生物标志物。 28 名 MCI 患者再次就诊，其中一半在 3-12 年内进展为 AD。结果：AD 中脑脊液总 (T)-tau、磷酸化 (P)-tau 和 A beta 42 水平出现预期变化，证实了这些生物标志物的诊断价值。我们还证实，CSF T-tau 和 P-tau 升高以及 APOE epsilon 4/epsilon 4 基因型存在时，从 MCI 进展为 AD 的风险增加，但 A beta 42 降低则不然。最后，我们首次证明，具有高 CSF T-tau 或 P-tau 和 APOE epsilon 4 纯合性的 MCI 受试者从 MCI 进展到 AD 的速度更快。结论：CSF T-tau 和 P-tau 以及 APOE epsilon 4/epsilon 4 基因型是 AD 的有力预测因子，并且还与从 MCI 到 AD 的更快进展相关。版权所有 (C) 2009 S. Karger AG，巴塞尔
Background/Aims: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta 42 (A beta 42) and the apolipoprotein E gene (APOE) epsilon 4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. Methods: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. Results: The expected changes in CSF total(T)-tau, phosphorylated (P)-tau and A beta 42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon 4/epsilon 4 genotype, but not with decreased A beta 42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon 4 homozygosity progressed faster from MCI to AD. Conclusions: CSF T-tau and P-tau as well as the APOE epsilon 4/epsilon 4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD. Copyright (C) 2009 S. Karger AG, Basel