Ultrastructure of ubiquitin-positive, TDP-43-negative neuronal inclusions in cerebral cortex of C9ORF72-linked frontotemporal lobar degeneration/amyotrophic lateral sclerosis

摘要

In a recent issue of Neuropathology, Troakes and colleagues described four cases of clinically pure motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) phenotype (without dementia) but with distinctive cortical and cerebellar pathology that were different from other proteinopathies of TDP-43 (transactive response DNS-binding protein of 43 kD).1 Neuronal inclusions (NCIs) in cerebral cortex, hippocampus and cerebellum were immuno-positive for p62, a ubiquitin-binding protein, but negative for TDP-43. The inclusions were also positive for ubiquitin, albeit weaker than p62. Genetic analysis showed that all cases contained the C9ORF72 repeat expansion, the recently reported cause of chromosome 9-linked ALS and frontotemporal dementia (c9FTD/ALS)