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Fig. 2 | Alzheimer's Research & Therapy

Fig. 2

From: Tau passive immunization blocks seeding and spread of Alzheimer hyperphosphorylated Tau-induced pathology in 3 × Tg-AD mice

Fig. 2

Alzheimer’s disease abnormally hyperphosphorylated Tau (AD p-Tau) templates the host Tau into neurofibrillary pathology in a time-dependent manner in triple-transgenic Alzheimer’s disease (3 × Tg-AD) mice. AD p-Tau (0.35 μg/2.5 μl saline) isolated from AD cerebral cortex was unilaterally injected into hippocampi of 11- to 12-month-old female 3 × Tg-AD mice. These animals shown in (a) and (b) were a separate group from those shown in Fig 1a and were employed solely to assess the time-dependent seeding activity and templating of the host Tau into neurofibrillary tangles in the ipsilateral hippocampus and spread of Tau pathology to the contralateral hippocampus. At 3 and 6 weeks after AD p-Tau injection, the animals were killed, and coronal sections of their brains were immunostained with AT8 (pSer202/pThr205) antibody. a Ipsilateral hippocampus at 3 weeks after AD p-Tau injection (left panel), contralateral side (middle panel), and ipsilateral side (right panel) at 6 weeks after AD p-Tau injection. CA1 area is marked by dashed lines. High-magnification images are shown as insets. Scale bar = 100 μm. b The number of AT8 intensely stained neurofibrillary tangles was counted from mice at 6 weeks after AD p-Tau injection (n = 2) at × 10 magnification. No tangles were observed in either the contralateral or ipsilateral side of mice at 3 weeks after AD p-Tau injection (n = 2). c The number of AT8 high-intensity neurofibrillary tangles was counted from mice at 7.5 weeks after AD p-Tau injection (AD p-Tau/immunoglobulin G [IgG]; n = 7) at × 10 magnification. d Immunostaining with AT8 for brain sections from AD p-Tau/IgG mice at 7.5 weeks after AD p-Tau injection. The contralateral hippocampus showed only a few tangles. Magnified views of boxed areas are shown. e Tau pathology load (AT8 and PHF-1) in CA1 neurons after AD p-Tau injection was significantly higher than that seen in a group (not shown in Fig. 1a) of 18-month-old naive 3 × Tg-AD mice (n = 3). f Bar graphs showing percentage of immune-positive area in somatodendritic compartment of CA1 pyramidal neurons at × 60 magnification. Not shown in this figure is that no primary antibody immunostaining controls were employed for both immunofluorescence and 3,3′-diaminobenzidine staining and were found to show only negative/background staining. Data are presented as mean ± SEM and analyzed by unpaired two-tailed Student’s t tests (n = 3 animals/group). *P < 0.05 compared with naive female 18-month-old 3 × Tg-AD mice. Scale bars = 1 mm for low magnification and 50 μm for higher magnification in (d); and scale bar = 20 μm in (e)

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