从 MCI 到 AD 的进展：CSF Aβ42 的预测价值受 APOE 基因型的影响。
Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype.
机构信息
Alzheimer Center and Department of Neurology, VU University Medical Center Amsterdam, The Netherlands.
出版信息
Neurobiol Aging. 2011 Aug;32(8):1372-8. doi: 10.1016/j.neurobiolaging.2009.08.006. Epub 2009 Sep 11.
OBJECTIVE
To study CSF biomarkers amyloid-beta 1-42 (Aβ42) and total tau (tau) in relation to APOE genotype in their ability to predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).
METHODS
In 100 MCI patients CSF Aβ42, tau and APOE genotype were determined. At follow-up of 18 (13-24) months 58 patients remained non-progressive and 42 progressed to AD.
RESULTS
Cox proportional hazards models showed an interaction between Aβ42 and APOE genotype (p<0.05). Stratification for APOE revealed HR (95% CI) for abnormal Aβ42 of 8.2 (2.1-31.9) for ε4 non-carriers, 3.9 (0.8-18.5) for heterozygotes and 0.3 (0.0-1.7) for homozygotes. Inversely, stratification for Aβ42 revealed that in patients with normal levels of Aβ42, ε4 homozygotes had a strongly increased risk of progression to AD with HR (95% CI) 20.8 (2.4-182.8). Tau and APOE independently predicted progression to AD.
CONCLUSIONS
Aβ42 was a stronger predictor of progression to AD in APOE ε4 non-carriers than in carriers. Furthermore, the risk of progression for ε4 homozygotes was very high, also in patients with normal levels of Aβ42.
目的
研究脑脊液生物标志物β淀粉样蛋白 1-42（Aβ42）和总 tau（tau）与 APOE 基因型在预测从轻度认知障碍（MCI）进展为阿尔茨海默病（AD）方面的关系。
方法
在 100 例 MCI 患者中，测定脑脊液 Aβ42、tau 和 APOE 基因型。在 18（13-24）个月的随访中，58 例患者病情无进展，42 例进展为 AD。
结果
Cox 比例风险模型显示 Aβ42 和 APOE 基因型之间存在交互作用（p<0.05）。APOE 分层显示异常 Aβ42 的 HR（95%CI）对于非 ε4 携带者为 8.2（2.1-31.9），杂合子为 3.9（0.8-18.5），纯合子为 0.3（0.0-1.7）。相反，对于 Aβ42 的分层显示，在 Aβ42 水平正常的患者中，ε4 纯合子进展为 AD 的风险显著增加，HR（95%CI）为 20.8（2.4-182.8）。tau 和 APOE 独立预测 AD 的进展。
结论
在 APOE ε4 非携带者中，Aβ42 是 AD 进展的更强预测因子，而在携带者中则不是。此外，即使在 Aβ42 水平正常的患者中，ε4 纯合子的进展风险也非常高。
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