Figure 3
Adeno-associated virus-ECD-Fc treatment reduces amyloid-beta levels in the brain of mice with Alzheimer’s disease at 12 months of age. (a) Compact amyloid-beta plaques were visualized with Congo red. Inset shows the representative morphology of Congo red-positive plaque at higher magnification. Scale bar=1mm. (b) Comparison of area fraction and plaque density of Congo red-stained plaques among groups. (c) The total amyloid-beta plaques stained with antibody 6E10 immunohistochemistry. Inset shows the representative morphology of 6E10-positive plaques at higher magnification. Scale bar=1 mm. (d) Comparison of area fraction and density of 6E10-positive plaques among groups. (e) Cerebral amyloid angiopathy was visualized with Congo red staining. Inset shows the morphology of cerebral amyloid angiopathy at higher magnification. Scale bar=1 mm. (f) Comparison of cerebral amyloid angiopathy and cerebral microbleed profiles among groups. (g) Co-localization of amyloid-beta plaque and ectodomain-Fc detected with amyloid-beta plaque staining (Congo red staining for top panels and Thioflavin S for bottom panels) and anti-human IgG Fc antibody. Scale bar: 200 μm (black), 40 μm (white). *shows co-localization of ectodomain-Fc with amyloid-beta plaques; # shows ectodomain-Fc expression in neurons. (h) Enzyme-linked immunosorbent assay analyses of Aβ40, Aβ42 and total Aβ of brain homogenates. 12mon-Con represents 12-month-old mice with Alzheimer’s disease treated with Adeno-associated virus-GFP (n=11); 12mon-Tre represents 12-month-old mice with Alzheimer’s disease treated with Adeno-associated virus-ectodomain-Fc at 9 months of age (n=9); 12mon-Pre represents 12-month-old mice with Alzheimer’s disease treated with Adeno-associated virus-ectodomain-Fc at 3 months of age (n=8); 9mon-Con represents 9-month-old mice with Alzheimer’s disease as baseline control for 12mon-Tre group (n=7). *P<0.05, **P<0.01 (mean±s.e.m., one-way analysis of variance, Tukey’s test).
