Molecular classification of amyotrophic lateral sclerosis by unsupervised clustering of gene expression in motor cortex

Eleonora Aronica, Frank Baas, Anand Iyer, Anneloor L.M.A. ten Asbroek, Giovanna Morello, Sebastiano Cavallaro*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

67 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, caused by the loss of motor neurons in the brain and spinal cord. Although 10% of ALS cases are familial (FALS), the majority are sporadic (SALS) and probably associated to a multifactorial etiology. Currently there is no cure or prevention for ALS. A prerequisite to formulating therapeutic strategies is gaining understanding of its etio-pathogenic mechanisms. In this study we analyzed whole-genome expression profiles of 41 motor cortex samples of control (10) and sporadic ALS (31) patients. Unsupervised hierarchical clustering was able to separate control from SALS patients. In addition, SALS patients were subdivided in two different groups that were associated to different deregulated pathways and genes, some of which were previously associated to familiar ALS. These experiments are the first to highlight the genomic heterogeneity of sporadic ALS and reveal new clues to its pathogenesis and potential therapeutic targets.

Original languageEnglish
Pages (from-to)359-376
Number of pages18
JournalNeurobiology of Disease
Volume74
DOIs
Publication statusPublished - 1 Feb 2015
Externally publishedYes

Bibliographical note

Publisher Copyright: © 2014.

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