Fig. 1: HAE-4 reduces parenchymal Aβ plaques and CAA in 5XE4 mice.

A, Schematic timeline of antibody treatment in 5XFAD (line 7031) x APOE4^+/+ (5XE4) mice with CAA assessed at 10-months-old. B–E, Representative immunostainings of HJ3.4B for mixed pan-Aβ pathology (B) and quantification of percent area in cortex of total Aβ (C), parenchymal Aβ plaques (D), and CAA (E). Control IgG, n = 13; HAE-4, n = 14, chi-Adu, n = 12. Scale bar = 750 μm. F–I, Thioflavin S (ThioS) staining for insoluble, fibrillar plaques (F) with quantification for area covered by total amyloid (G), parenchymal plaques (H), and CAA (I) pathology in overlaying cortex (Control IgG, n = 12; HAE-4, n = 14, chi-Adu, n = 12). Scale bar = 750 μm. J, K, Insoluble Aβ₄₀ (J) or Aβ₄₂ (K) protein concentrations from bulk cortical tissue lysate homogenized in guanidine measured by ELISA and normalized to total protein concentration in cortex (Control IgG, n = 13; HAE-4, n = 14, chi-Adu, n = 12). L–O, Forebrain vessel isolation paradigm using dextran gradient centrifugation of a separate 5XE4 cohort treated with antibodies (L; Control IgG, n = 13; HAE-4, n = 12, chi-Adu, n = 13). Isolated brain vasculature fluorescently stained for X34⁺ fibrillar CAA, endothelial marker CD31, and nuclei marker TOPRO3. Scale bar = 150 μm. (M). Insoluble Aβ₄₀ (N) and Aβ₄₂ (O) protein concentrations assessed by ELISA from forebrain-extracted vessels sonicated in guanidine-HCL and normalized to total protein concentration. Control = Control IgG. Chi-Adu = Chimeric Aducanumab. Data expressed as mean ± SEM, one-way ANOVA with Tukey’s post hoc test (two-sided) performed for all statistical analyses except Kruskal-Wallis test with Dunn’s multiple comparisons test (two-sided) for parenchymal Aβ/ThioS, and Aβ₄₀ analysis (D, H, J). *P < 0.05, **P < 0.01. No other statistical comparisons are significant unless indicated.