Fig. 3: Lecanemab induces phagocytosis of Aβ and alleviates downstream consequences of Aβ pathology through Fc-mediated microglial effector functions. | Nature Neuroscience

Fig. 3: Lecanemab induces phagocytosis of Aβ and alleviates downstream consequences of Aβ pathology through Fc-mediated microglial effector functions.

From: The Alzheimer’s therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia

Fig. 3: Lecanemab induces phagocytosis of Aβ and alleviates downstream consequences of Aβ pathology through Fc-mediated microglial effector functions.The alternative text for this image may have been generated using AI.

a, Flow cytometry analysis of Methoxy-X04+ cells within the hCD45+ population (microglia) after 8 weeks of Lecanemab (red) or IgG1 (black) treatment. The x axis represents Methoxy-X04 fluorescence intensity, while the y axis shows the number of cells. The overlaid histograms (black and red) highlight differences in Methoxy-X04 staining levels. b, Percentage of X04+ microglia (CD45+) isolated from IgG1 or Lecanemab-treated mice (unpaired two-sided t-test; IgG1, n = 8 mice; Lec, n = 7 mice). c, Percentage of X04+ microglia (CD45+, CD68high) isolated from IgG1 or Lecanemab-treated mice (unpaired two-sided t-test; IgG1, n = 8 mice; Lec, n = 7 mice). d, Representative super-resolution confocal images of synaptic loss surrounding X-34+ plaques in IgG1-treated, Lecanemab-treated and Lecanemab LALA-PG-treated xenotransplanted mice. Synaptic puncta were defined as synaptophysin (magenta) and Homer1 (green) immunoreactive puncta (white) around X-34+ plaques (cyan). Scale bar = 10 µm. e–g, Quantification of synaptophysin (one-way ANOVA, NS; e), Homer1 (one-way ANOVA, P = 0.044; f) and synaptic puncta (one-way ANOVA, NS; g), in peri-plaque area (defined as 5 µm from the X-34 edges; IgG1, n = 10 mice; Lec, n = 12 mice; Lec LALA-PG, n = 9 mice). h, Representative confocal images for IBA1 (magenta), X-34 (yellow) and LAMP1 (blue) in sagittal brain sections from AppNL-G-F Csf1rΔFIRE/ΔFIRE mice xenotransplanted with human-derived microglia and treated with IgG1, Lecanemab and Lecanemab LALA-PG; scale bars = 1 mm, insets = 250 µm. The area of LAMP1 was assessed in the 10-µm rings surrounding X-34 (peri-plaque region) and then divided by the area of the brain section or the peri-plaque area. i,j, Quantification of LAMP1 area expressed as percentage of the total brain section (i) and the peri-plaque area (j); (i) one-way ANOVA (P = 0.0091) and (j) one-way ANOVA (NS; IgG1, n = 10 mice; Lec, n = 12 mice; Lec LALA-PG, n = 9 mice). k, Quantification of IBA1 area expressed as percentage of the total brain section (Kruskal–Wallis test, NS; IgG1, n = 10 mice; Lec, n = 12 mice; Lec LALA-PG, n = 9 mice). Mean ± s.e.m. shown for each group and points represent individual animals. Square symbols, males; triangle, females.

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