Spread of pathology in amyotrophic lateral sclerosis: assessment of phosphorylated TDP-43 along axonal pathways

摘要

IntroductionThe progression of amyotrophic lateral sclerosis (ALS) through the brain has recently been staged using independent neuropathological and neuroimaging modalities. The two schemes tie into the concept of pathological spread through corticofugal axonal transmission that stems from observation of oligodendrocyte pTDP-43 aggregates along with neuronal inclusions. Here, we aimed to assess evidence of transmission along axonal pathways by looking for pTDP-43 oligodendrocyte pathology in involved white matter tracts, and to present a first validation of the neuropathological staging scheme.pTDP-43 immunohistochemistry was performed in select white matter tracts and grey matter regions from the staging scheme in postmortem-confirmed ALS cases (N = 34). Double-labelling immunofluorescence was performed to confirm co-localisation of pTDP-43 immunoreactivity to oligodendrocytes.