Riemenschneider M, Mahmoodzadeh S, Eisele T, Klopp N, Schwarz S, Wagenpfeil S, Diehl J, Mueller U, Foerstl H, Illig T, Kurz A
Department of Psychiatry, Neurochemistry and Neurogenetics Laboratory, TU-München Ismaningerstr. 22, 81675 München, Germany.
Neurobiol Aging. 2004 Nov-Dec;25(10):1305-8. doi: 10.1016/j.neurobiolaging.2004.01.001.
Epidemiological studies identified a higher risk of developing Alzheimer's disease (AD) among subjects with elevated cholesterol levels. This association may be caused by a modulation of the amyloid precursor protein (APP) processing in response to the cellular cholesterol content. High cholesterol levels may favor the amyloidogenic pathway by inhibition of the alpha-secretase probably leading to elevated beta-Amyloid (Abeta) production. The identification of a linkage peak on chromosome 10q using high Abeta as quantitative trait led us to examine polymorphisms of genes located on chromosome 10 involved in cholesterol metabolism, like Lipase A (LIPA), Cholesterol 25 hydroxylase (CH25H), and FLJ22476, a high density lipoprotein binding related protein. Using 286 patients with AD and 162 controls we analyzed several single nucleotide polymorphisms (SNPs) within LIPA, CH25H, and FLJ22476. None of the polymorphisms showed significant association with AD which contradicts recent findings on CH25H. From our results we conclude that the investigated genetic variations do not contribute to the genetic risk of AD.
流行病学研究表明，胆固醇水平升高的人群患阿尔茨海默病（AD）的风险更高。这种关联可能是由于细胞胆固醇含量对淀粉样前体蛋白（APP）加工过程的调节所致。高胆固醇水平可能通过抑制α-分泌酶而有利于淀粉样蛋白生成途径，这可能导致β-淀粉样蛋白（Aβ）产生增加。以高Aβ作为数量性状，在10号染色体上鉴定出一个连锁峰，这促使我们研究位于10号染色体上参与胆固醇代谢的基因的多态性，如脂肪酶A（LIPA）、胆固醇25羟化酶（CH25H）以及与高密度脂蛋白结合相关的蛋白FLJ22476。我们对286例AD患者和162例对照进行研究，分析了LIPA、CH25H和FLJ22476内的几个单核苷酸多态性（SNP）。这些多态性均未显示与AD有显著关联，这与最近关于CH25H的研究结果相矛盾。根据我们的研究结果，我们得出结论，所研究的基因变异对AD的遗传风险没有影响。
