The multistep hypothesis of ALS revisited

著者: Adriano Chiò, Letizia Mazzini, Sandra D’Alfonso, Lucia Corrado, Antonio Canosa, Cristina Moglia, Umberto Manera, Enrica Bersano, Maura Brunetti, Marco Barberis, Jan H. Veldink, Leonard H. van den Berg, Neil Pearce, William Sproviero, Russell L. McLaughlin, Alice Vajda, Orla Hardiman, James Rooney, Gabriele Mora, Andrea Calvo, Ammar Al‐Chalabi - Neurology 2018 被引用: 216

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) incidence rates are consistent with the hypothesis that ALS is a multistep process. We tested the hypothesis that carrying a large effect mutation might account for ≥1 steps through the effect of the mutation, thus leaving fewer remaining steps before ALS begins. METHODS: genes was performed in 82% of incident cases. As confirmation, we used data from ALS cases diagnosed in the Republic of Ireland (2006-2014). We regressed the log of age-specific incidence against the log of age with least-squares regression for the subpopulation carrying disease-associated variation in each separate gene. RESULTS: . CONCLUSION: The identification of a reduced number of steps in patients with ALS with genetic mutations compared to those without mutations supports the idea of ALS as a multistep process and is an important advance for dissecting the pathogenic process in ALS.