Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Department of Neurology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2023 Aug 19;24(16):12966. doi: 10.3390/ijms241612966.
Alzheimer's disease (AD) is the most common neurodegenerative disease, with a complex genetic background. Apart from rare, familial cases, a combination of multiple risk loci contributes to the susceptibility of the disease. Genome-wide association studies (GWAS) have identified numerous AD risk loci. Changes in cerebrospinal fluid (CSF) biomarkers and imaging techniques can detect AD-related brain changes before the onset of clinical symptoms, even in the presence of preclinical mild cognitive impairment. In this study, we aimed to assess the associations between SNPs in well-established GWAS AD risk loci and CSF biomarker levels or cognitive test results in Slovenian patients with cognitive decline. The study included 82 AD patients, 28 MCI patients with pathological CSF biomarker levels and 35 MCI patients with normal CSF biomarker levels. Carriers of at least one polymorphic rs157581 C allele had lower Aβ ( = 0.033) and higher total tau ( = 0.032) and p-tau levels ( = 0.034). Carriers of at least one polymorphic T allele in rs1358030 had lower total tau ( = 0.019), while polymorphic rs1416406 allele was associated with lower total tau ( = 0.013) and p-tau ( = 0.036). In addition, carriers of at least one polymorphic T allele in rs1803274 had lower cognitive test scores ( = 0.029). The study findings may contribute to the identification of genetic markers associated with AD and MCI and provide insights into early disease diagnostics.
阿尔茨海默病（AD）是最常见的神经退行性疾病，具有复杂的遗传背景。除了罕见的家族性病例外，多个风险基因座的组合导致了疾病的易感性。全基因组关联研究（GWAS）已经确定了许多 AD 风险基因座。脑脊液（CSF）生物标志物和影像学技术的变化可以在临床症状出现之前检测到与 AD 相关的大脑变化，即使在存在临床前轻度认知障碍的情况下也是如此。在这项研究中，我们旨在评估在斯洛文尼亚认知能力下降的患者中，GWAS 确定的 AD 风险基因座中的 SNP 与 CSF 生物标志物水平或认知测试结果之间的关联。该研究包括 82 名 AD 患者、28 名 CSF 生物标志物水平异常的 MCI 患者和 35 名 CSF 生物标志物水平正常的 MCI 患者。至少携带一个多态性 rs157581 C 等位基因的携带者具有较低的 Aβ（ = 0.033）和较高的总 tau（ = 0.032）和 p-tau 水平（ = 0.034）。至少携带一个多态性 rs1358030 的 T 等位基因的携带者具有较低的总 tau（ = 0.019），而多态性 rs1416406 等位基因与较低的总 tau（ = 0.013）和 p-tau（ = 0.036）相关。此外，至少携带一个多态性 rs1803274 的 T 等位基因的携带者具有较低的认知测试分数（ = 0.029）。研究结果可能有助于确定与 AD 和 MCI 相关的遗传标记，并为早期疾病诊断提供见解。
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