Early-onset axonal pathology in a novel P301S-Tau transgenic mouse model of frontotemporal lobar degeneration

Neuropathology and Applied Neurobiology
Janet van EerselLars M Ittner

Abstract

Tau becomes hyperphosphorylated in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD-tau), resulting in functional deficits of neurones, neurofibrillary tangle (NFT) formation and eventually dementia. Expression of mutant human tau in the brains of transgenic mice has produced different lines that recapitulate various aspects of FTLD-tau and AD. In this study, we characterized the novel P301S mutant tau transgenic mouse line, TAU58/2. Both young and aged TAU58/2 mice underwent extensive motor testing, after which brain tissue was analysed with immunohistochemistry, silver staining, electron microscopy and Western blotting. Tissue from various FTLD subtypes and AD patients was also analysed for comparison. TAU58/2 mice presented with early-onset motor deficits, which became more pronounced with age. Throughout the brains of these mice, tau was progressively hyperphosphorylated resulting in increased NFT formation with age. In addition, frequent axonal swellings that stained intensively for neurofilament (NF) were present in young TAU58/2 mice prior to NFT formation. Similar axonal pathology was also observed in human FTLD-tau and AD. Interestingly, activated microglia were found in close proximity to neurones ...Continue Reading

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Citations

Feb 2, 2016·Neurobiology of Learning and Memory·Ann van der JeugdJürgen Götz
Aug 16, 2016·Neuroscience Letters·Magdalena PrzybylaJanet van Eersel
Oct 14, 2016·PloS One·Annika van HummelLars M Ittner
Nov 1, 2016·Molecular Neurobiology·Ya-Qing LiLan Tan
May 28, 2019·Journal of Neuropathology and Experimental Neurology·Claire H StevensLezanne Ooi
Jul 30, 2020·Acta Neuropathologica·Arne IttnerLars M Ittner
Jan 7, 2017·Acta Neuropathologica·Rachel H TanGlenda M Halliday
Aug 16, 2019·Acta Neuropathologica·Luis Aragão GomesDietmar Rudolf Thal
Nov 26, 2019·Neurobiology of Disease·Hank ChengAndrew M Schumacher

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