Ewers Michael, Zhong Zhenyu, Bürger Katharina, Wallin Anders, Blennow Kaj, Teipel Stefan J, Shen Yong, Hampel Harald
Department of Psychiatry, Alzheimer Memorial Center, Ludwig-Maximilian University, Munich, Germany.
Brain. 2008 May;131(Pt 5):1252-8. doi: 10.1093/brain/awn034. Epub 2008 Mar 11.
The Apolipoprotein (ApoE) epsilon 4 allele is a major genetic risk factor of Alzheimer's disease, and may affect the production of amyloid beta (A beta(1-42)). Recently, we have shown that beta-secretase (BACE 1) activity can be reliably detected within the brain and human CSF. Here, we have examined an association between the ApoE genotype and CSF-levels of BACE 1 activity in Alzheimer's disease and mild cognitive impairment (MCI). A total of 148 subjects were included: 60 Alzheimer's disease patients, 51 MCI subjects and 37 elderly healthy controls. The CSF-levels of A beta(1-42), BACE 1 activity and BACE protein were measured in all of these subjects. The differences between ApoE-epsilon 4 carriers and ApoE-epsilon 4 non-carriers in these CSF-based measures were determined controlling for gender, age and MMSE score. The ApoE-epsilon 4 genotype was associated with increased BACE 1 activity in both Alzheimer's disease (P = 0.03) and MCI (P = 0.04) subjects. Levels of A beta(1-42) were decreased in ApoE-epsilon 4 carriers in MCI (P = 0.004) but not Alzheimer's disease subjects. This study is the first to demonstrate the association between ApoE-epsilon 4 and CSF-BACE 1 activity in MCI and Alzheimer's disease subjects. The assessment of BACE 1 in CSF may provide a sensitive measure to detect in vivo alterations in the amyloidogenic processing potentially modified by the ApoE genotype.
载脂蛋白（ApoE）ε4等位基因是阿尔茨海默病的主要遗传风险因素，可能影响β淀粉样蛋白（Aβ(1-42)）的产生。最近，我们已经表明，β-分泌酶（BACE 1）活性能够在大脑和人类脑脊液中被可靠地检测到。在此，我们研究了阿尔茨海默病和轻度认知障碍（MCI）患者中ApoE基因型与脑脊液中BACE 1活性水平之间的关联。总共纳入了148名受试者：60名阿尔茨海默病患者、51名MCI受试者和37名老年健康对照者。对所有这些受试者测量了脑脊液中Aβ(1-42)、BACE 1活性和BACE蛋白水平。在控制性别、年龄和MMSE评分的情况下，确定了这些基于脑脊液的测量指标中ApoE-ε4携带者和非携带者之间的差异。ApoE-ε4基因型与阿尔茨海默病（P = 0.03）和MCI（P = 0.04）受试者中BACE 1活性增加相关。在MCI的ApoE-ε4携带者中Aβ(1-42)水平降低（P = 0.004），但在阿尔茨海默病受试者中未降低。本研究首次证明了ApoE-ε4与MCI和阿尔茨海默病受试者脑脊液中BACE 1活性之间的关联。脑脊液中BACE 1的评估可能提供一种敏感的测量方法，以检测可能被ApoE基因型改变的淀粉样蛋白生成过程中的体内变化。
