Gámez-Valero Ana, Campdelacreu Jaume, Vilas Dolores, Ispierto Lourdes, Gascón-Bayarri Jordi, Reñé Ramón, Álvarez Ramiro, Armengol Maria P, Borràs Francesc E, Beyer Katrin
Department of Pathology, Germans Trias i Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain.
REMAR-IVECAT Group, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Barcelona, Spain.
Biomedicines. 2021 Sep 20;9(9):1272. doi: 10.3390/biomedicines9091272.
Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer's disease (AD), and presents pathological and clinical overlap with both AD and Parkinson's disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.
路易体痴呆(DLB)是继阿尔茨海默病(AD)之后最常见的退行性痴呆病因之一,并且在病理和临床方面与AD及帕金森病(PD)均存在重叠。因此,每三例DLB病例中只有一例能得到正确诊断。血小板先前被认为与神经退行性变有关,其包含的微小RNA(miRNA)分析可能会提供疾病生物标志物。在此,我们对DLB患者和健康对照者的全血小板miRNA转录组进行了分析。在2017年至2019年连续开展的三项研究中,对162名个体(包括DLB、AD和PD患者以及健康对照者)进一步验证了差异表达的miRNA。结果得到了一个由七种miRNA组成的生物标志物,其在区分DLB和AD方面显示出最高的诊断潜力。此外,与对照相比,DLB中有两种miRNA下调,AD中有四种miRNA上调,PD中有两种miRNA下调。预测性靶标分析确定了由于血小板miRNA失调导致的三个疾病特异性通路簇。我们的横断面研究评估了一种基于血小板相关miRNA的新型、高度特异性和敏感性生物标志物的识别,该生物标志物可区分DLB和AD。