Hippocampal aggregation signatures of pathogenic UBQLN2 in amyotrophic lateral sclerosis and frontotemporal dementia.

ABSTRACT: Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterized by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial amyotrophic lateral sclerosis and/or frontotemporal dementia cases not caused by UBQLN2 pathogenic variants, particularly C9orf72-linked cases. This makes the mechanistic role of mutant ubiquilin 2 protein and the value of ubiquilin 2 pathology for predicting genotype unclear. Here we examine a cohort of 44 genotypically diverse amyotrophic lateral sclerosis cases with or without frontotemporal dementia, including eight cases with UBQLN2 variants [resulting in p.S222G, p.P497H, p.P506S, p.T487I (

SUBMITTER: Thumbadoo KM 

PROVIDER: S-EPMC11449146 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature