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. 2016 Jul 4;7:12082. doi: 10.1038/ncomms12082

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(a) Gallyas-Braak silver staining of tau tangles in brain sections of Tau4R-AP mice at 12 (n=3), 18 (n=4), and 25 months of age (n=6). The sections were counterstained with fast red. The right panels are Tau4R mice at 25 months of age (n=6). The brain regions are cerebral cortex (CT); hippocampus (HP); olfactory bulb (OB); striatum (STR); thalamus (TH); hypothalamus (HY); midbrain (MB); Pons; Medulla (MY), and cerebellum (CB). Tau tangles could be detected in Tau4R-AP, but not Tau4R, mice at 18 months of ages, and the accumulation of tangles were dramatically increased with aging and spread to other brain regions (25 months of age, third column), except in cerebellum (bottom panel). Scale bar, 50 μm. (b) Immunohistochemical analysis showed age-dependent spreading of endogenous tau tangle in Tau4R-AP mice (n=13) using antibodies specific to endogenous phosphorylated S422 of tau (pS422). The brain regions are cerebral cortex (CT); hippocampus (HP); olfactory bulb (OB); striatum (STR); thalamus (TH); hypothalamus (HY); midbrain (MB); Pons; Medulla (MY), and cerebellum (CB). While no signal was detected in Tau4R mice (n=6) even at 25 months of age, tau tangles first appeared in cortical and hippocampal region (18 months of age, second column) of Tau4R-AP mice and spread to other brain region with aging (25 months of age, third column), except in cerebellum (bottom panel). Scale bar, 50 μm.