"Prion-Like" Templated Misfolding in Tauopathies

• Published in: Brain pathology (Zurich, Switzerland) Vol. 23; no. 3; pp. 342 - 349
• Main Authors: Clavaguera, Florence, Lavenir, Isabelle, Falcon, Ben, Frank, Stephan, Goedert, Michel, Tolnay, Markus
• Format: Journal Article
• Language: English
• Published: Switzerland Blackwell Publishing Ltd 01-05-2013; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Alzheimer's disease; Animals; Humans; MINI‐SYMPOSIUM: “Prion‐Like” Templated Misfolding in Neurodegenerative Disorders; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; prion disease; Prion Diseases - genetics; Prion Diseases - metabolism; prion-like aggregation; Proteins; Proteostasis Deficiencies - genetics; Proteostasis Deficiencies - metabolism; Proteostasis Deficiencies - therapy; tau protein; tauopathies; Tauopathies - genetics; Tauopathies - metabolism; Tauopathies - therapy; templated misfolding
• ISSN: 1015-6305; 1750-3639; 1750-3639
• DOI: 10.1111/bpa.12044

The soluble microtubule‐associated protein tau forms hyperphosphorylated, insoluble and filamentous inclusions in a number of neurodegenerative diseases referred to as “tauopathies.” In Alzheimer's disease, tau pathology develops in a stereotypical manner, with the first lesions appearing in the locus coeruleus and entorhinal cortex, from where they appear to spread to the hippocampus and neocortex. Propagation of tau pathology is also a characteristic of argyrophilic grain disease, where the tau lesions spread throughout the limbic system. Significantly, isoform composition and morphology of tau filaments can differ between tauopathies, suggesting the existence of distinct tau strains. Extensive experimental findings indicate that prion‐like mechanisms underly the pathogenesis of tauopathies.