Fyn depletion ameliorates tauP301L-induced neuropathology

The Src family non-receptor tyrosine kinase Fyn has been implicated in neurodegeneration of Alzheimer's disease through interaction with amyloid [beta] (A[beta]). However, the role of Fyn in the pathogenesis of primary tauopathies such as FTDP-17, where A[beta] plaques are absent, is poorly und...

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Bibliographic Details
Published in:Acta neuropathologica communications 2020-07, Vol.8 (1), p.1-108, Article 108
Main Authors: Liu, Guanghao, Fiock, Kimberly L, Levites, Yona, Golde, Todd E, Hefti, Marco M, Lee, Gloria
Format: Article
Language:English
Subjects:
Alzheimer's disease
Aprotinin
Brain
Fyn
Genetic aspects
Genetic engineering
Hydrocephalus
Kinases
Laboratories
Mutation
Neurodegeneration
Neurofibrillary tangles
Pathogenesis
Proteins
Rodents
Tau
Tyrosine
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Summary:The Src family non-receptor tyrosine kinase Fyn has been implicated in neurodegeneration of Alzheimer's disease through interaction with amyloid [beta] (A[beta]). However, the role of Fyn in the pathogenesis of primary tauopathies such as FTDP-17, where A[beta] plaques are absent, is poorly understood. In the current study, we used AAV2/8 vectors to deliver tau.sup.P301L to the brains of WT and Fyn KO mice, generating somatic transgenic tauopathy models with the presence or absence of Fyn. Although both genotypes developed tau pathology, Fyn KO developed fewer neurofibrillary tangles on Bielschowsky and Thioflavin S stained sections and showed lower levels of phosphorylated tau. In addition, tau.sup.P301L-induced behavior abnormalities and depletion of synaptic proteins were not observed in the Fyn KO model. Our work provides evidence for Fyn being a critical protein in the disease pathogenesis of FTDP-17. Keywords: Fyn, Tau, Neurofibrillary tangles
ISSN:2051-5960
2051-5960
DOI:10.1186/s40478-020-00979-6