Altered microRNAs related to synaptic function as potential plasma biomarkers for Alzheimer’s disease

Alzheimer's Research & Therapy

Isabel Hernández¹  Merce Boada²  Alberto Lleó³  Jordi Clarimon³  Judit Català-Solsona⁴  Cristina Fábregas⁴  Alfredo J. Miñano-Molina⁴  Dolores Siedlecki-Wullich⁴  Carlos A. Saura⁴  José Rodríguez-Álvarez⁵ 

[1] 0000 0001 2325 3084, grid.410675.1, Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain;0000 0004 1762 4012, grid.418264.d, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;0000 0001 2325 3084, grid.410675.1, Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain;0000 0004 1762 4012, grid.418264.d, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;grid.7080.f, Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain;grid.7080.f, Institut de Neurociències and Dpt. Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain;0000 0004 1762 4012, grid.418264.d, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;grid.7080.f, Institut de Neurociències and Dpt. Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain;0000 0004 1762 4012, grid.418264.d, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;0000000121791997, grid.251993.5, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 10461, New York, NY, USA;

关键词: Alzheimer’s disease;    Mild cognitive impairment;    Synapses;    miRNAs;    Plasma;    Human;    Biomarker;    Frontotemporal dementia;   

DOI  :  10.1186/s13195-019-0501-4

来源: publisher

【 摘 要 】

BackgroundSeveral evidences suggest that failure of synaptic function occurs at preclinical stages of Alzheimer’s disease (AD) preceding neuronal loss and the classical AD pathological hallmarks. Nowadays, there is an urgent need to identify reliable biomarkers that could be obtained with non-invasive methods to improve AD diagnosis at early stages. Here, we have examined plasma levels of a group of miRNAs related to synaptic proteins in a cohort composed of cognitive healthy controls (HC), mild cognitive impairment (MCI) and AD subjects.MethodsPlasma and brain levels of miRNAs were analysed in two different cohorts including 38 HC, 26 MCI, 56 AD dementia patients and 27 frontotemporal dementia (FTD) patients. D’Agostino and Pearson and Shapiro-Wilk tests were used to evaluate data normality. miRNA levels between groups were compared using a two-sided nonparametric Mann-Whitney test and sensitivity and specificity was determined by receiver operating characteristic curve analysis.ResultsSignificant upregulation of miR-92a-3p, miR-181c-5p and miR-210-3p was found in the plasma of both MCI and AD subjects. MCI patients that progress to AD showed higher plasma levels of these miRNAs. By contrast, no changes in miR-92a-3p, miR-181c-5p or miR-210-3p levels were observed in plasma obtained from a cohort of FTD.ConclusionOur study shows that plasma miR-92a-3p, miR-181c-5p and miR-210-3p constitute a specific molecular signature potentially useful as a potential biomarker for AD.

【 授权许可】

CC BY