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Prion-like propagation as a pathogenic principle in frontotemporal dementia.
Journal article

Prion-like propagation as a pathogenic principle in frontotemporal dementia.

  • Hock EM Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Polymenidou M Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • 2016-08-10
Published in:
  • Journal of neurochemistry. - 2016
FTD
FUS
TDP-43
prion-like spread
tau
Brain
Frontotemporal Dementia
Humans
Prion Diseases
Prions
English 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. Frontotemporal dementia (FTD) is a progressive neurodegenerative disease causing severe personality dysfunctions, characterized by profound heterogeneity. Accumulation of tau, TDP-43 or FUS cytoplasmic aggregates characterize molecularly distinct and non-overlapping FTD subtypes. Here, we discuss the current evidence suggesting that prion-like propagation and cell-to-cell spread of each of these cytoplasmic aggregates may underlie disease progression and heterogeneity. This article is part of the Frontotemporal Dementia special issue.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.rero.ch/global/documents/153279
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