Affiliations: [a] AXON Neuroscience R&D Services SE, Bratislava, Slovakia
| [b]
Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
| [c] AXON Neuroscience SE, Larnaca, Cyprus
Correspondence:
[*]
Correspondence to: Rostislav Skrabana or Michal Novak, Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 84510 Bratislava, Slovakia. Tel.: +421 254788100; Fax: +421 54774276; E-mails: [email protected] (R. Skrabana); [email protected] (M. Novak).
Abstract: Animal models of neurodegeneration induced by neuronal expression of truncated tau protein emerge as an important tool for understanding the pathogenesis of human tauopathies and for therapy development. Here we highlight common features of truncated tau models and make a critical assessment of possible pitfalls in their analysis. Particularly, the amount of soluble tau oligomers, which are suspected to be neurotoxic agents participating on the spreading of pathology inside the brain, may be overestimated due to a post-lysis oxidative tau oligomerization. Using a mouse brain lysate spiked with recombinant truncated and full length tau forms, we show that tau oligomers might inadvertently be produced during the isolation procedure. This finding is further corroborated by the analysis of brain lysates originated from a mouse model expressing truncated tau variant. Our results underline the necessity of thiol-protecting conditions during the analysis of tau oligomers involved in the etiopathogenesis of various tauopathies including Alzheimer’s disease.
Keywords: Alzheimer’s disease, protein tau, tauopathy, transgenic models
