Kirschling Chartika M, Kölsch Heike, Frahnert Christine, Rao Marie Luise, Maier Wolfgang, Heun Reinhard
Department of Psychiatry, University of Bonn, Germany.
Neuroreport. 2003 Jul 1;14(9):1243-6. doi: 10.1097/00001756-200307010-00011.
Pathological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and amyloid-beta (Abeta) plaques. Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. BACE (beta-site APP cleaving enzyme) was identified as the beta-secretase. Variations of the BACE gene might influence activity and function of the protein and, thus, might influence the pathogenesis of AD. Consequently, we investigated the association of different BACE polymorphisms with AD. BACE exon 5 polymorphism influenced the risk of AD. This effect was most pronounced in apolipoprotein E4 allele carriers. Furthermore, Abeta(42) CSF levels were influenced by BACE genotype. It appears that BACE polymorphism plays a more important role in the development of AD than previously assumed, possibly by influencing Abeta(42) levels.
阿尔茨海默病（AD）的病理特征是神经原纤维缠结和β-淀粉样蛋白（Aβ）斑块。Aβ是由β-分泌酶和γ-分泌酶切割淀粉样前体蛋白产生的。BACE（β-位点APP切割酶）被鉴定为β-分泌酶。BACE基因的变异可能会影响该蛋白的活性和功能，进而可能影响AD的发病机制。因此，我们研究了不同BACE基因多态性与AD的关联。BACE外显子5多态性影响AD的风险。这种效应在载脂蛋白E4等位基因携带者中最为明显。此外，BACE基因型会影响脑脊液中Aβ（42）的水平。看来BACE基因多态性在AD的发展中所起的作用比之前认为的更为重要，可能是通过影响Aβ（42）水平来实现的。
