Guoqiao Wang, United States of America
Washington University School of Medicine in Saint Louis Division of BiostatisticsAuthor Of 1 Presentation
REGIONAL EFFECTS OF GANTENERUMAB ON NEUROIMAGING MARKERS IN THE DOMINANTLY INHERITED ALZHEIMER NETWORK TRIALS UNIT (DIAN-TU)
Abstract
Aims
To evaluate treatment effects of anti-amyloid antibody Gantenerumab on neuroimaging outcomes in individuals carrying autosomal dominant mutations in PSEN1, PSEN2, APP genes enrolled in the DIAN-TU
Methods
Participants were randomized into drug (n=52) or placebo arms (n=40) and received up to 48 months of drug treatment. Longitudinal structural MRI, [11C]-Pittsburgh Compound B (PiB) PET, and [18F]-fluorodeoxyglucose (FDG) PET imaging data were processed using FreeSurfer and the PET Unified Pipeline (PUP) and analyzed using linear mixed effects models. Models estimated the longitudinal effects of Gantenerumab treatment on imaging outcomes of the DIAN-TU trial.
Results
Treatment significantly reduced the longitudinal increase of mean cortical PiB PET signal (β = -.06, SE = .01, t = -5.83, p < .0001), but did not affect the additional imaging endpoints of precuneus FDG (β = -.01, SE = .005, t = -1.579, p = .118) or precuneus thickness (β = .003, SE = .007, t = 0.388, p = .69). Estimated effects on PiB PET varied regionally in a pattern distinct from baseline PiB PET levels (Figure 1).
Conclusions
Gantenerumab successfully lowered levels of beta-amyloid as indexed by PiB PET imaging. The regional pattern of drug effects suggest clearance is not solely driven by baseline levels of pathology. The observed pattern may be influenced by Gantenerumab having a differential impact on diffuse versus dense-core beta-amyloid plaques or variability in blood brain barrier permeability that may lead to differential local concentration of the drug.