TDP ‐43 in amyotrophic lateral sclerosis – is it a prion disease?

Amyotrophic lateral sclerosis is a devastating disease characterized by rapidly progressive paresis. The neuropathological hallmark of most amyotrophic lateral sclerosis cases are neuronal and glial aggregates of phosphorylated 43‐kDa TAR DNA ‐binding protein ( pTDP ‐43). The accumulation of similar proteins into insoluble aggregates is now recognized as a common pathological hallmark of neurodegenerative diseases in general. Importantly, many of these proteins such as tau and amyloid‐β in Alzheimer's disease and α‐synuclein in Parkinson's show a stereotypical sequential distribution pattern with progressing disease. In this review, we discuss recent evidence that TDP ‐43 in ALS may propagate similarly to other neurodegenerative disease proteins. We furthermore delineate similarities and important differences of TDP ‐43 proteinopathies to prion diseases.