Prion-like propagation as a pathogenic principle in frontotemporal dementia

Frontotemporal dementia is a devastating neurodegenerative disease causing stark alterations in personality and language. Characterized by severe atrophy of the frontal and temporal brain lobes, frontotemporal dementia (FTD) shows extreme heterogeneity in clinical presentation, genetic causes, and pathological findings. Like most neurodegenerative diseases, the initial symptoms of FTD are subtle, but increase in severity over time, as the disease progresses. Clinical progression is paralleled by exacerbation of pathological findings and the involvement of broader brain regions, which currently lack mechanistic explanation. Yet, a flurry of studies indicate that protein aggregates accumulating in neurodegenerative diseases can act as propagating entities, amplifying their pathogenic conformation, in a way similar to infectious prions. In this prion-centric view, FTD can be divided into three subtypes, TDP-43 or FUS proteinopathy and tauopathy. Here, we review the current evidence that FTD-linked pathology propagates in a prion-like manner and discuss the implications of these findings for disease progression and heterogeneity.