title: Serum microRNAs in sporadic amyotrophic lateral sclerosis.
abstract: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA "fingerprints" are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. Moreover, our results indicate a more heterogeneous molecular etiology of sporadic ALS compared with (mono)genic cases, which should be considered for the development of disease modifying treatments.
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Freischmidt
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Müller
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zondler
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weydt
authors.affiliation: Institute for Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mayer
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Christine A F
authors.initials: CA
authors.lastname: von Arnim
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Hübers
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Dorst
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
authors.affiliation: Genomics-Core Facility, University Hospital Ulm, Center for Biomedical Research, Ulm, Germany.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Holzmann
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Danzer
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany. Electronic address: jochen.weishaupt@uni-ulm.de.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Weishaupt
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000235:genetics*; D016000:Cluster Analysis; D015331:Cohort Studies; D019295:Computational Biology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D046228:Microarray Analysis; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Amyotrophic lateral sclerosis; Biomarker; Diagnosis; MicroRNA; Serum