Babić Leko Mirjana, Španić Popovački Ena, Willumsen Nanet, Nikolac Perković Matea, Pleić Nikolina, Zubčić Klara, Langer Horvat Lea, Vogrinc Željka, Boban Marina, Borovečki Fran, Zemunik Tatijana, de Silva Rohan, Šimić Goran
Department for Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
Reta Lila Weston Institute, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, London, United Kingdom.
Front Mol Neurosci. 2024 Sep 25;17:1456670. doi: 10.3389/fnmol.2024.1456670. eCollection 2024.
Genetic studies have shown that variants in the microtubule-associated protein tau () gene, which encodes tau protein, can increase the risk for Alzheimer's disease (AD). Additionally, two haplotypes of the gene (H1 and H2) are associated with various neurodegenerative disorders, including AD. This study aimed to test the association of haplotypes (H1 and H2) and haplotype-tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del-In9, rs7521) with AD.
The study included 964 individuals: 113 with AD, 53 with mild cognitive impairment (MCI), 54 with other dementias, and 744 healthy controls.
The results showed that individuals carrying the A allele in the rs1467967 polymorphism, the GG genotype in the rs7521 polymorphism, and the G allele in the rs242557 polymorphism had worse performance on various neuropsychological tests. Carriers of the C allele in rs2471738 polymorphism and CC homozygotes also showed worse performance on neuropsychological tests and pathological levels of several cerebrospinal fluid (CSF) biomarkers. However, T allele carriers in the rs2471738 polymorphism were more represented among patients with dementia and apolipoprotein E () ɛ4 carriers. Carriers of the H2 haplotype had worse performance on various neuropsychological tests, consistent with our previous study, which associated the H2 haplotype with pathological levels of CSF AD biomarkers. Regarding the rs3785883 polymorphism, further research is needed since both the AA and GG genotypes were associated with pathological levels of CSF and plasma AD biomarkers.
In conclusion, further genetic studies are needed to elucidate the role of haplotypes and haplotype-tagging polymorphisms in the development of AD.
基因研究表明，编码tau蛋白的微管相关蛋白tau（）基因中的变异可增加患阿尔茨海默病（AD）的风险。此外，该基因的两种单倍型（H1和H2）与包括AD在内的各种神经退行性疾病相关。本研究旨在测试tau单倍型（H1和H2）以及tau单倍型标签多态性（rs1467967、rs242557、rs3785883、rs2471738、del-In9、rs7521）与AD的关联。
该研究纳入了964名个体：113名AD患者、53名轻度认知障碍（MCI）患者、54名其他痴呆患者和744名健康对照者。
结果显示，在tau rs1467967多态性中携带A等位基因、在tau rs7521多态性中携带GG基因型以及在tau rs242557多态性中携带G等位基因的个体在各种神经心理学测试中的表现较差。rs2471738多态性中C等位基因的携带者和CC纯合子在神经心理学测试以及几种脑脊液（CSF）生物标志物的病理水平上也表现较差。然而，rs2471738多态性中T等位基因的携带者在痴呆患者和载脂蛋白E（）ɛ4携带者中更为常见。H2 tau单倍型的携带者在各种神经心理学测试中的表现较差，这与我们之前的研究一致，即H2 tau单倍型与CSF AD生物标志物的病理水平相关。关于rs3785883多态性，由于AA和GG基因型均与CSF和血浆AD生物标志物的病理水平相关，因此需要进一步研究。
总之，需要进一步的基因研究来阐明tau单倍型和tau单倍型标签多态性在AD发病中的作用。
