Fig. 6

a Simulated clinical outcomes in ADAS-Cog in a 78-week trial with mild-to-moderate AD patients with low amyloid baseline (amyloid load negative) after BACE inhibition (verubecestat), gamma-secretase inhibition (semagacestat) and solanezumab (Sola) antibody. Differences with placebo values shown. BACE-I results in a substantial worsening over the whole trial duration, with a somewhat lower negative effect of GSI and almost no effect of solanezumab. b Simulated clinical outcomes in ADAS-Cog in a 78-week trial with mild-to-moderate AD patients with medium to high amyloid baseline (amyloid load positive) after BACE inhibition (verubecestat), gamma-secretase inhibition (semagacestat) and solanezumab antibody. Differences with placebo values are shown. BACE-I improves cognition, with substantial benefit (1–2 points) at longer time points, while GSI has a smaller dose-dependent response (1–1.5 points). Note that higher BACE inhibition is less beneficial. Solanezumab, on the contrary, has a modest dose-dependent clinical benefit (0.5–1 points) ADAS-Cog Alzheimer Disease Assessment Scale, cognitive subscale, BACE-I BACE inhibitor, GSI gamma-secretase inhibitor, wks weeks