Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes.

ABSTRACT:

Objective

A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.

Methods

A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.

Results

The 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1^WT in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VA

SUBMITTER: Forsberg K 

PROVIDER: S-EPMC6691870 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature