Galimberti Daniela, Villa Chiara, Fenoglio Chiara, Serpente Maria, Ghezzi Laura, Cioffi Sara M G, Arighi Andrea, Fumagalli Giorgio, Scarpini Elio
Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
J Alzheimers Dis. 2014;42(4):1261-7. doi: 10.3233/JAD-140756.
Several micro(mi)RNA are deregulated in brain, cerebrospinal fluid (CSF), and serum/plasma from patients with Alzheimer's disease (AD). The aim of the study was to profile circulating miRNAs in serum as non-invasive biomarkers for AD, correlating them with those identified in CSF, the biological fluid which better reflects biochemical changes occurring during pathological processes in the brain and may provide a robust indicator of AD-related disease pathogenesis thanks to the evidence of low amyloid and high levels of tau and hyperphosphorylated tau. Using a two-step analysis (array and validation through real-time PCR), a down-regulation (mean fold change ± SEM) of miR-125b (0.415 ± 0.11 versus 1.381 ± 0.36, p = 0.009), miR-23a (0.111 ± 0.03 versus 0.732 ± 0.14, p < 0.001), and miR-26b (0.414 ± 0.11 versus 1.353 ± 0.39, p < 0.01), out of 84 tested, was shown in serum from 22 AD patients compared with 18 non-inflammatory and 8 inflammatory neurological controls (NINDCs and INDCs) and 10 patients with frontotemporal dementia. Significant down-regulation of miR-125b and miR-26b was also confirmed in CSF from AD patients versus NINDCs (miR-125b: 0.089 ± 0.03 versus 0.230 ± 0.08, p < 0.001; miR-26b: 0.217 ± 0.06 versus 1.255 ± 0.29, p < 0.001, mean fold change ± SEM, respectively), whereas data were not replicated for miR-23a. In serum, miR-125b had an AUC of 0.82 to distinguish AD from NINDCs (95% CI: 0.65-0.98, p = 0.005). In conclusion, we demonstrated that cell-free miR-125b serum levels are decreased in serum from patients with AD as compared with NINDC and distinguish between AD and NINDCs with an accuracy of 82%.
在阿尔茨海默病（AD）患者的大脑、脑脊液（CSF）和血清/血浆中，几种微小（mi）RNA的表达失调。本研究的目的是分析血清中循环miRNA，将其作为AD的非侵入性生物标志物，并将它们与在CSF中鉴定出的miRNA相关联。CSF是一种生物体液，能更好地反映大脑病理过程中发生的生化变化，并且由于淀粉样蛋白水平低、tau蛋白和过度磷酸化tau蛋白水平高的证据，可能为AD相关疾病的发病机制提供有力指标。采用两步分析法（阵列分析和实时PCR验证），在22例AD患者的血清中，与18例非炎症性和8例炎症性神经疾病对照（NINDCs和INDCs）以及10例额颞叶痴呆患者相比，在84种检测的miRNA中，miR-125b（平均倍数变化±SEM）下调（0.415±0.11对1.381±0.36，p = 0.009）、miR-23a（0.111±0.03对0.732±0.14，p < 0.001）和miR-26b（0.414±0.11对1.353±0.39，p < 0.01）。与NINDCs相比，AD患者CSF中miR-125b和miR-26b也有显著下调（miR-125b：0.089±0.03对0.230±0.08，p < 0.001；miR-26b：0.217±0.06对1.255±0.29，p < 0.001，分别为平均倍数变化±SEM），而miR-23a的数据未得到重复验证。在血清中，miR-125b区分AD与NINDCs的曲线下面积（AUC）为0.82（95%CI：0.65 - 0.98，p = 0.005）。总之，我们证明与NINDC相比，AD患者血清中无细胞miR-125b水平降低，其区分AD和NINDCs的准确率为82%。
