Bruno Francesco, Aceto Mirella A, Paparazzo Ersilia, Arcuri Domenico, Vozzo Francesca, Mirante Serena, Greco Beatrice M, Serra Cassano Teresa, Abondio Paolo, Canterini Sonia, Malvaso Antonio, Grecucci Alessandro, Citrigno Luigi, Geracitano Silvana, Spadafora Patrizia, Puccio Gianfranco, Frangipane Francesca, Curcio Sabrina M, Ferrise Francesca, Laganà Valentina, Colao Rosanna, Passarino Giuseppe, Bruni Amalia C, Maletta Raffaele, Cavalcanti Francesca, Montesanto Alberto
Department of Human and Social Sciences, Faculty of Social and Communication Sciences, Universitas Mercatorum, Rome, Italy.
Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy.
PLoS One. 2025 May 6;20(5):e0309631. doi: 10.1371/journal.pone.0309631. eCollection 2025.
Recent studies have highlighted the significant role of ADAM17/TACE (encoded by ADAM17/TACE) in the pathogenesis of Alzheimer's disease (AD). Yet, the relationship between ADAM17/TACE gene polymorphisms and AD was less studied. This study aims to analyse the relationship of ADAM17/TACE gene polymorphism with the risk, age of onset, neuropsychiatric manifestations, cognitive impairment, and medial temporal lobe atrophy in sporadic AD (sAD). This case-control association study was conducted in an Italian cohort consisting of 297 sAD patients and 316 controls. Seven tag-SNPs were selected and genotyped. Linear and logistic regression analyses were used to assess the association between parameters of interest and the genetic variability of ADAM17/TACE. After Bonferroni correction, our findings underscore the complexity of genetic influences of ADAM17/TACE on sAD, particularly the roles of rs12692385 in modulating sAD risk and the performance on the Rey Auditory Verbal Learning Test - delayed recall. In addition, rs13008101 significantly affected the performance on the Clock Drawing Test. Moreover, rs10179642 and rs35280016 were associated with a higher frequency and severity of hallucinations and agitation/aggression, respectively. These results contribute to a deeper understanding of the genetic underpinnings of sAD and may be useful for examining the risk of developing sAD, assessing cognitive deficits, neuropsychiatric symptoms, and informing new therapeutic strategies and future research targeting ADAM17/TACE.
最近的研究突出了ADAM17/TACE（由ADAM17/TACE编码）在阿尔茨海默病（AD）发病机制中的重要作用。然而，ADAM17/TACE基因多态性与AD之间的关系研究较少。本研究旨在分析ADAM17/TACE基因多态性与散发性AD（sAD）的风险、发病年龄、神经精神表现、认知障碍和内侧颞叶萎缩之间的关系。这项病例对照关联研究在一个意大利队列中进行，该队列由297例sAD患者和316例对照组成。选择了7个标签单核苷酸多态性（tag-SNP）并进行基因分型。采用线性和逻辑回归分析来评估感兴趣的参数与ADAM17/TACE基因变异性之间的关联。经过Bonferroni校正后，我们的研究结果强调了ADAM17/TACE对sAD遗传影响的复杂性，特别是rs12692385在调节sAD风险以及对雷伊听觉词语学习测验延迟回忆表现方面的作用。此外，rs13008101显著影响了画钟测验的表现。而且，rs10179642和rs35280016分别与幻觉的较高频率和严重程度以及激越/攻击行为相关。这些结果有助于更深入地了解sAD的遗传基础，可能有助于检查患sAD的风险、评估认知缺陷、神经精神症状，并为针对ADAM17/TACE的新治疗策略和未来研究提供参考。
