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Expression of non-neuronal Tau in humans and mice

Lekka, C.; Ellis, M.; Holden, K.; Flaxman, C. S.; Todd, J. A.; Stefana, I. M.; Richardson, S. J.

2026-03-02 cell biology
10.64898/2026.02.27.708441 bioRxiv
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BackgroundTau, encoded by the microtubule-associated protein tau gene (MAPT), is traditionally associated with neuronal function in maintaining cytoskeletal stability and regulating intracellular transport. Its dysregulation is implicated in a range of neurodegenerative disorders. Beyond its well-established high levels of expression in neurons of the central and peripheral nervous systems, increasing evidence indicates that Tau is also expressed in non-neuronal cells/tissues such as muscle, kidney, testis, and pancreas, albeit at much lower levels than in neurons. However, the assessment of low levels of non-neuronal Tau requires that the specificities of the anti-Tau antibodies used are fully validated. MethodsThree previously validated anti-Tau antibodies (Tau-12, Tau-1, RD3) were used to test Tau expression levels in 33 mouse and 66 human tissues using Food and Drug Administration-quality tissue microarrays in immunocytochemistry and western blot analyses. ResultsThe presence of Tau was confirmed in salivary gland, kidney, skeletal muscle, heart, pancreas and oesophagus in both human and mouse tissues. ConclusionsDysregulation of Tau protein expression and alterations in its post-translational modification is a causative factor in neurodegenerative disease. We have demonstrated a wider Tau expression in other tissues and cells, outside the brain, which may be dysregulated in other diseases.

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