Division of Neuropsychology, Institute of Psychology, University of Zurich, Binzmühlestr. 14/25, 8050 Zurich, Switzerland.
Neurobiol Aging. 2011 Jun;32(6):1023-32. doi: 10.1016/j.neurobiolaging.2009.07.001. Epub 2009 Aug 3.
There is evidence that brain cholesterol metabolism modulates the vulnerability for Alzheimer's disease (AD). Previous data showed that brain β-amyloid load in elderly subjects with the CYP46 (cholesterol 24S-hydroxylase) TT-positive genotype was higher than in CYP46 TT-negative elderly subjects. We investigated effects of the CYP46 T/C polymorphism on parahippocampal and hippocampal grey matter (GM) morphology in 81 young subjects using structural magnetic resonance imaging based morphometry. We found that young TT-homozygotes exhibited smallest and CC-homozygotes largest parahippocampal and hippocampal GM volumes with the volumes of the CT-heterozygotes ranging in between. Parahippocampal and hippocampal volumes were positively correlated with delayed memory performance in C-carriers and negatively with immediate memory performance in TT-homozygotes. It has been shown that the brain cholesterol metabolism in general modulates dendrite outgrowth, synaptogenesis, and neuron survival, and it was suggested that CYP46 indirectly influences β-amyloid metabolism. CYP46 C-carriers are privileged both in terms of β-amyloid metabolism and in terms of brain reserve due to their larger parahippocampal and hippocampal structures. The exact cellular mechanisms that translate the CYP46 allelic variation into volumetric brain differences in the parahippocampal gyrus and hippocampus are still unknown and need to be further investigated.
有证据表明，大脑胆固醇代谢调节阿尔茨海默病（AD）的易感性。先前的数据表明，在 CYP46（胆固醇 24S-羟化酶）TT 阳性基因型的老年受试者中，大脑 β-淀粉样蛋白负荷高于 CYP46 TT 阴性的老年受试者。我们使用基于结构磁共振成像的形态计量学研究了 CYP46 T/C 多态性对 81 名年轻受试者的海马旁回和海马灰质（GM）形态的影响。我们发现 TT 纯合子的海马旁回和海马 GM 体积最小，CC 纯合子的海马旁回和海马 GM 体积最大，CT 杂合子的 GM 体积介于两者之间。海马旁回和海马 GM 体积与 C 携带者的延迟记忆表现呈正相关，与 TT 纯合子的即刻记忆表现呈负相关。一般来说，大脑胆固醇代谢调节树突生长、突触形成和神经元存活，有人认为 CYP46 间接影响 β-淀粉样蛋白代谢。由于其较大的海马旁回和海马结构，CYP46 C 携带者在 β-淀粉样蛋白代谢和大脑储备方面都具有优势。将 CYP46 等位基因变异转化为海马旁回和海马灰质体积差异的确切细胞机制尚不清楚，需要进一步研究。
