Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes

INTRODUCTION: Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (A beta) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented.METHODS: Sixty-five apolipoprotein E epsilon 4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 mu g (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up A beta positron emission tomography (PET) scans at 18 to 24 months.RESULTS: CAD106 induced measurable serum A beta immunoglobulin G titers in 41/42 participants, slower rates of A beta plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic).DISCUSSION: Despite early termination, these findings support the potential value of conducting larger prevention trials of A beta active immunotherapies in individuals at risk for AD.