Strafella Claudia, Caputo Valerio, Termine Andrea, Fabrizio Carlo, Calvino Giulia, Megalizzi Domenica, Ruffo Paola, Toppi Elisa, Banaj Nerisa, Bassi Andrea, Bossù Paola, Caltagirone Carlo, Spalletta Gianfranco, Giardina Emiliano, Cascella Raffaella
Genomic Medicine Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
Medical Genetics Laboratory, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
Front Aging Neurosci. 2022 Feb 17;14:821789. doi: 10.3389/fnagi.2022.821789. eCollection 2022.
Amnestic mild cognitive impairment (aMCI) and sporadic Alzheimer's disease (AD) are multifactorial conditions resulting from a complex crosstalk among multiple molecular and biological processes. The present study investigates the association of variants localized in genes and miRNAs with aMCI and AD, which may represent susceptibility, prognostic biomarkers or multi-target treatment options for such conditions. We included 371 patients (217 aMCI and 154 AD) and 503 healthy controls, which were genotyped for a panel of 120 single nucleotide polymorphisms (SNPs) and, subsequently, analyzed by statistical, bioinformatics and machine-learning approaches. As a result, 21 SNPs were associated with aMCI and 13 SNPs with sporadic AD. Interestingly, a set of variants shared between aMCI and AD displayed slightly higher Odd Ratios in AD with respect to aMCI, highlighting a specific risk trajectory linking aMCI to AD. Some of the associated genes and miRNAs were shown to interact within the signaling pathways of APP (Amyloid Precursor Protein), ACE2 (Angiotensin Converting Enzyme 2), miR-155 and PPARG (Peroxisome Proliferator Activated Receptor Gamma), which are known to contribute to neuroinflammation and neurodegeneration. Overall, results of this study increase insights concerning the genetic factors contributing to the neuroinflammatory and neurodegenerative mechanisms underlying aMCI and sporadic AD. They have to be exploited to develop personalized approaches based on the individual genetic make-up and multi-target treatments.
遗忘型轻度认知障碍（aMCI）和散发性阿尔茨海默病（AD）是由多种分子和生物学过程之间复杂的相互作用导致的多因素病症。本研究调查了基因和微小RNA（miRNA）中定位的变异与aMCI和AD的关联，这些变异可能代表此类病症的易感性、预后生物标志物或多靶点治疗选择。我们纳入了371例患者（217例aMCI和154例AD）和503名健康对照，对一组120个单核苷酸多态性（SNP）进行基因分型，随后采用统计、生物信息学和机器学习方法进行分析。结果显示，21个SNP与aMCI相关，13个SNP与散发性AD相关。有趣的是，aMCI和AD之间共享的一组变异在AD中的优势比相对于aMCI略高，突出了一条将aMCI与AD联系起来的特定风险轨迹。一些相关基因和miRNA在APP（淀粉样前体蛋白）、ACE2（血管紧张素转换酶2）、miR - 155和PPARG（过氧化物酶体增殖物激活受体γ）的信号通路中相互作用，已知这些通路会导致神经炎症和神经退行性变。总体而言，本研究结果增加了我们对导致aMCI和散发性AD潜在神经炎症和神经退行性变机制的遗传因素的认识。必须利用这些结果来开发基于个体基因组成的个性化方法和多靶点治疗。
