A CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects

NEUROBIOLOGY OF AGING

卷:32

Article

Haenggi, Juergen^1,2  Mondadori, Christian R. A.³  Buchmann, Andreas⁴  Henke, Katharina⁵  Hock, Christoph² 

[1] Univ Zurich, Div Neuropsychol, Inst Psychol, CH-8050 Zurich, Switzerland

[2] Psychiat Univ Hosp Zurich, Div Psychiat Res, CH-8032 Zurich, Switzerland

[3] Univ Zurich Hosp, Dept Neurol, Neuropsychol Unit, CH-8091 Zurich, Switzerland

[4] Univ Zurich, Childrens Hosp, CH-8032 Zurich, Switzerland

[5] Univ Bern, Dept Psychol, CH-3000 Bern 9, Switzerland

关键词: Cholesterol metabolism;    Single nucleotide polymorphism;    CYP46 (cholesterol 24S-hydroxylase);    Parahippocampal and hippocampal morphology;    Alzheimer's disease;    Voxel-based morphometry;    Healthy young subjects;    Brain reserve capacity;    Amyloid-beta;   

DOI  :  10.1016/j.neurobiolaging.2009.07.001

来源: Elsevier

【 摘 要 】

There is evidence that brain cholesterol metabolism modulates the vulnerability for Alzheimer's disease (AD). Previous data showed that brain beta-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 beta-amyloid metabolism. CYP46 C-carriers are privileged both in terms of beta-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. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

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