Reduced Soluble Ubiquilin2 in Amyotrophic Lateral Sclerosis Carrying Ubiquilin2 (P494L) Mutation: Clinicopathological and Biochemical Evidence From an Autopsy Case

Summary We report on the clinicopathological and biochemical features at autopsy of a patient with familial amyotrophic lateral sclerosis carrying an Ubiquilin2 (UBQLN2) P494L mutation. Neuropathologically, there were widespread TDP‐43‐positive inclusions in the whole brain, especially upper and lower motor neurons, limbic systems and hippocampus; Ubiquilin2‐positive intranuclear inclusions were also present. Biochemically, the UBQLN2 mutation patient showed TDP‐43 Type B inclusions and decreased UBQLN2 expression. These findings support the hypothesis that loss of function of UQBLN2 is linked to the formation of TDP‐43 inclusions.