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. 2021 Jan 23;144(3):963–974. doi: 10.1093/brain/awaa445

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© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Aged P301SxTAU62^on-off mice show decreased hyperphosphorylated and fibrillar tau pathology compared to their heterozygous littermates. Histological tests comparing AT8 stained brainstem sections (A) of 16-month-old P301Shet (n = 7) and P301SxTAU62^on-off (abbreviated P62^on-off) mice (n = 7) revealed that the different performance in the behavioural tests was paralleled by different degrees of hyperphoshorylated tau pathology (B, P = 3.39 × 10⁻⁶). These results were also mirrored by Gallyas-stained brainstem sections (C) of 16-month-old P301Shet (n = 7), and P301SxTAU62^on-off mice (n = 7), which revealed different degrees of fibrillar tau pathology between the two groups (D, P = 7.77 × 10⁻⁵). ***P < 0.001. Scale bar = 200 µm (A and C). See also Supplementary Table 2.