Differential Involvement of Optineurin in Amyotrophic Lateral Sclerosis With or Without SOD1 Mutations

Background: Mutations in optineurin have recently been linked to amyotrophic lateral sclerosis (ALS). Objective: To determine whether optineurin-positive skeinlike inclusions are a common pathologic feature in ALS, including SOD1-linked ALS. Design: Clinical case series. Setting: Academic referral center. Subjects: We analyzed spinal cord sections from 46 clinically and pathologically diagnosed ALS cases and ALS transgenic mouse models overexpressing ALS-linked SOD1 mutations G93A or L126Z. Results: We observed optineurin-immunoreactive skeinlike inclusions in all the sporadic ALS and familial ALS cases without SOD1 mutation, but not in cases with SOD1 mutations or in transgenic mice overexpressing the ALS-linked SOD1 mutations G93A or L126Z. Conclusion: The data from this study provide evidence that optineurin is involved in the pathogenesis of sporadic ALS and non-SOD1 familial ALS, thus supporting the hypothesis that these forms of ALS share a pathway that is distinct from that of SOD1-linked ALS.