Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. panos.alexopoulos @ lrz.tum.de
Dement Geriatr Cogn Disord. 2011;32(3):164-70. doi: 10.1159/000332017. Epub 2011 Oct 13.
Recently, genetic variants of the neuronal sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) have emerged as risk factors for the development of Alzheimer's disease (AD).
In this study, SORL1 gene polymorphisms, which have been shown to be related to AD, were analyzed for associations with cerebrospinal fluid (CSF) amyloid beta1-42 (Aβ(1-42)), phosphorylated tau181, and total tau levels in a non-Hispanic Caucasian sample, which encompassed 100 cognitively healthy elderly individuals, 166 patients with mild cognitive impairment, and 87 patients with probable AD. The data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). Moreover, the impact of gene-gene interactions between SORL1 single nucleotide polymorphisms (SNPs) and the apolipoprotein E (APOE) ε4 allele, the major genetic risk factor for sporadic AD, on Aβ(1-42) concentrations was investigated.
Significant associations between CSF Aβ(1-42) levels and the SORL1 SNPs 23 (rs3824968) and 24 (rs2282649) were detected in the AD group. The latter association became marginally statistically insignificant after Bonferroni correction for multiple comparisons. Carriers of the SORL1 SNP24 T allele and the SNP23 A allele both had lower CSF Aβ(1-42) concentrations than non-carriers of these alleles. The analysis of the impact of interactions between APOE ε4 allele and SORL1 SNPs on CSF Aβ(1-42) levels unraveled significant influences of APOE.
Our findings provide further support for the notion that SORL1 genetic variants are related to AD pathology, probably by regulating the amyloid cascade.
神经元 SORL1 相关受体 A 型重复基因（SORL1，也称为 LR11 或 sorLA）的遗传变异最近被认为是阿尔茨海默病（AD）发病的危险因素。
本研究分析了与 AD 相关的 SORL1 基因多态性与脑脊液（CSF）β淀粉样蛋白 1-42（Aβ（1-42））、磷酸化 tau181 和总 tau 水平之间的关系，该研究纳入了 100 名认知健康的老年个体、166 名轻度认知障碍患者和 87 名可能的 AD 患者。数据来自阿尔茨海默病神经影像学倡议（ADNI）数据库（www.loni.ucla.edu/ADNI）。此外，还研究了 SORL1 单核苷酸多态性（SNP）与载脂蛋白 E（APOE）ε4 等位基因（散发性 AD 的主要遗传危险因素）之间的基因-基因相互作用对 Aβ（1-42）浓度的影响。
在 AD 组中，CSF Aβ（1-42）水平与 SORL1 SNP23（rs3824968）和 SNP24（rs2282649）显著相关。经多重比较 Bonferroni 校正后，后者的相关性变得略有统计学意义。与这些等位基因非携带者相比，SORL1 SNP24 T 等位基因和 SNP23 A 等位基因携带者的 CSF Aβ（1-42）浓度均较低。分析 APOE ε4 等位基因与 SORL1 SNP 相互作用对 CSF Aβ（1-42）水平的影响，揭示了 APOE 的显著影响。
我们的研究结果进一步支持了 SORL1 遗传变异与 AD 病理相关的观点，可能是通过调节淀粉样蛋白级联反应。
