• Progressive hyperphosphorylation of Tau has been extensively characterized biochemically and immunohistochemically, using a multitude of phospho-epitope antibodies
• A profound NFT-like pathology is observed in the cortex, hippocampus, brainstem and spinal cord
• Progressive astrocytosis and microgliosis, leading to neuronal loss
• Cognitive impairment in Morris water maze paradigm and age-dependent hippocampal LTP deficit as of 3.5 months
• Correlation of motoric impairment and survival with Tau hyperphosphorylation
• Correlation of motoric impairment with spinal cord pathology

Age dependent increase of Tau pathology (AT8 = pSer202 pThr205 Tau) in the frontal cortex, as measured by IHC (mean ± SEM, n = 10).

Progressive rotarod performance deficit, starting from 4 months of age. Time on the rod at a fixed speed of 10 rpm was measured (mean ± SEM, n = 15). Statistics: Two-way ANOVA, Sidak’s multiple comparison.

Long term potentiation deficit (induced by a high frequency stimulation) in the CA1 region of the hippocampus in 3.5 month old TAU[P301S] animals and age-matched controls (mean ± SEM, n = 5 per group). Statistics: Welches’ unpaired t test

Describing papers:

• Original paper: Allen et al., 2002: Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. DOI: 10.1523/JNEUROSCI.22-21-09340.2002
• Koivisto et al., 2019: Progressive age-dependent motor impairment in human tau P301S overexpressing mice. DOI: 10.1016/j.bbr.2019.112158
• Van Olst et al. 2020: Microglial activation arises after aggregation of phosphorylated-tau in a neuron-specific P301S tauopathy model. DOI: 10.1016/j.neurobiolaging.2020.01.003
• Hamton et al., 2010: Cell-mediated neuroprotection in a mouse model of human tauopathy. DOI: 10.1523/JNEUROSCI.0834-10.2010
• Belluci et al., 2004: Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. DOI: 10.1016/S0002-9440(10)63421-9
• Xu et al, 2014: Memory deficits correlate with tau and spine pathology in P301S MAPT transgenic mice. DOI: 10.1111/nan.12160

Therapeutic intervention papers:

• Chai et al, 2011: Passive immunization with anti-Tau antibodies in two transgenic models: reduction of Tau pathology and delay of disease progression. DOI: 10.1074/jbc.M111.229633
• Ozcelik et al. 2013: Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice. DOI: 10.1371/journal.pone.0062459