Borroni Barbara, Grassi Mario, Costanzi Chiara, Archetti Silvana, Caimi Luigi, Padovani Alessandro
Centre for Ageing Brain and Dementia, Department of Neurology, the III Laboratory of Biotechnology and Department of Biochemistry, University of Brescia, Brescia, Italy.
Am J Geriatr Psychiatry. 2006 Dec;14(12):1022-31. doi: 10.1097/01.JGP.0000225088.29353.08. Epub 2006 Sep 6.
APOE is the most recognized genetic risk factor for sporadic late-onset Alzheimer disease (AD). The role of APOE genotype in Lewy body dementia (LBD) is still unknown as well as the relationship between APOE genotype and cholesterol levels.
The objective of this study was to explore the association between APOE genotype and cholesterol levels in patients with LBD and those with AD.
Eighty-two patients with LBD were consecutively enrolled as well as a comparable number of patients with AD and comparison group. Each subject underwent a clinical and neuropsychologic evaluation and APOE genotyping.
The distribution of APOE genotypes significantly differed between AD and LBD cases compared with the comparison group, with the APOE epsilon4+ (epsilon4+/epsilon4 + or epsilon4+/epsilon4-) genotype more frequent in patient subgroups. Different models have been fitted, and total APOE epsilon4-hypercholesterolemia complete interaction effect was claimed in predicting their relationship on disease outcome. Subjects with hypercholesterolemia and heterozygous for APOE epsilon4 allele had more than threefold risk to develop AD compared both with the comparison group and with those with LBD. The risk to develop AD in hypercholesterolemic and APOE epsilon4 homozygous subjects was 13-fold compared with the comparison group and those with LBD. Conversely, there was not evidence for APOE epsilon4-hypercholesterolemia complete interaction effect in LBD and in the comparison group.
This study highlighted that APOE is a risk factor not only for AD, but also for LBD, and that the APOE-cholesterol pathway differently affects AD and LBD. This approach may aid the search for the identification of an interactive effect of APOE genotype and modifiable risk factors, i.e., hypercholesterolemia, eventually resulting in individualized and effective cholesterol-lowering therapy in at-risk subjects.
载脂蛋白E（APOE）是散发性晚发型阿尔茨海默病（AD）最公认的遗传风险因素。APOE基因型在路易体痴呆（LBD）中的作用以及APOE基因型与胆固醇水平之间的关系仍不清楚。
本研究旨在探讨LBD患者和AD患者中APOE基因型与胆固醇水平之间的关联。
连续纳入82例LBD患者以及数量相当的AD患者和对照组。每位受试者均接受临床和神经心理学评估以及APOE基因分型。
与对照组相比，AD和LBD病例中APOE基因型的分布存在显著差异，APOE ε4+（ε4+/ε4+或ε4+/ε4-）基因型在患者亚组中更为常见。采用了不同的模型，并且在预测其对疾病结局的关系时，总APOE ε4-高胆固醇血症完全交互作用效应得到证实。与对照组和LBD患者相比，高胆固醇血症且APOE ε4等位基因杂合的受试者患AD的风险高出三倍以上。与对照组和LBD患者相比，高胆固醇血症且APOE ε4纯合的受试者患AD的风险为13倍。相反，在LBD和对照组中没有证据表明存在APOE ε4-高胆固醇血症完全交互作用效应。
本研究强调APOE不仅是AD的风险因素，也是LBD的风险因素，并且APOE-胆固醇途径对AD和LBD的影响不同。这种方法可能有助于寻找APOE基因型与可改变的风险因素（即高胆固醇血症）的交互作用，最终为高危受试者带来个性化且有效的降胆固醇治疗。
