Effects of an Amyloid-Binding Antibody in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaque accumulation and vascular dysfunction. Antibody therapies targeting Aβ, including Lecanemab (mAb158, Lec), have been shown to reduce plaque burden, but the effect of these antibodies in a mouse model of amyloid deposition is unclear. We examined the effects of Lec in 5xFAD mice, an AD model with early and extensive Aβ deposition. We hypothesized that Lec would reduce high Aβ burden but not affect regions of inflammation. Body weight changes significantly differed between untreated and treated groups, while cognitive testing showed no benefits with treatment. Pilot H&E and PB staining revealed no overt hemorrhagic pathology following treatment. 6E10 staining demonstrated region-dependent plaque burden, greatest in the inner cortex (IC) and ventral/dorsal striatum (VS/DS) and lowest in the hippocampus (HC). However, there was a significant decrease in Aβ deposition only in the HC of female Lec-treated 5xFAD. GFAP staining showed significant increases in inflammation in the IC of female Lec-treated 5xFAD and in the HC of male Lec-treated 5xFAD. These findings suggest that treatment with Lec has some effect on decreasing Aβ burden and may increase inflammation.