Variable tau accumulation in murine models with abnormal prion protein deposits

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:383

Article

Piccardo, Pedro¹  King, Declan¹  Brown, Deborah¹  Barron, Rona M.¹ 

[1] Univ Edinburgh, Roslin Inst & RDSVS, Easter Bush EH25 9RG, Midlothian, Scotland

关键词: Prion diseases;    Tau protein;    Transgenic models;    Neurodegeneration;    Complex proteinopathies;   

DOI  :  10.1016/j.jns.2017.10.040

来源: Elsevier

【 摘 要 】

The conversion of cellular prion protein (PrP) into a misfolded isoform is central to the development of prion diseases. However, the heterogeneous phenotypes observed in prion disease may be linked with the presence of other misfolded proteins in the brain. While hyperphosphorylated tau (p.tau) is characteristic of Alzheimer's disease (AD), p.tau is also observed in human prion diseases. To explore this association in the absence of potential effects due to aging, drug treatment, agonal stage and postmortem delay we analyzed p.tau and PrP immunopositivity in mouse models. Analyses were performed on mice inoculated with prion agents, and mice with PrP amyloid in the absence of prion disease. We observed that p.tau was consistently present in animals with prion infectivity (models that transmit disease upon serial passage). In contrast, p.tau was very rarely observed or absent in mice with PrP amyloid plaques in the absence of prion replication. These data indicate that the formation of p.tau is not linked to deposition of misfolded PrP, but suggest that the interaction between replication of infectivity and host factors regulate the formation of p.tau and may contribute to the heterogeneous phenotype of prion diseases.

【 授权许可】

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