RT Journal Article SR Electronic T1 Transcriptional Signatures of Synaptic Vesicle Genes Define Myotonic Dystrophy Type I Neurodegeneration JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.17.208132 DO 10.1101/2020.07.17.208132 A1 Jimenez-Marin, Antonio A1 Diez, Ibai A1 Labayru, Garazi A1 Sistiaga, Andone A1 Sepulcre, Jorge A1 Lopez de Munain, Adolfo A1 Cortes, Jesus M. YR 2020 UL http://biorxiv.org/content/early/2020/07/17/2020.07.17.208132.abstract AB Despite significant research, the biological mechanisms underlying the brain degeneration in Myotonic Dystrophy Type I (DM1) remain largely unknown. Here we have assessed brain degeneration by measuring the volume loss (VL) and cognitive deficits (CD) in two cohorts of DM1 patients, and associating them to the large-scale brain transcriptome maps provided by the Allen Human Brain Atlas (AHBA). From a list of preselected hypothesis-driven genes, three of them appear to play a major role in degeneration: dystrophin (DMD), alpha-synuclein (SNCA) and the microtubule-associated protein tau (MAPT). Moreover, a purely data-driven strategy identified gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. Therefore, by combining large-scale transcriptome interactions with brain imaging and cognitive function, we provide a new more comprehensive understanding of DM1 that might help define future therapeutic strategies and research into this condition.Competing Interest StatementThe authors have declared no competing interest.