Use of Donanemab in Early Symptomatic Alzheimer Disease / Reply

Pomara and Imbimbo comment on the study on the use of donanemab in early symptomatic Alzheimer disease. The TRAILBLAZER-ALZ 2 trial 1 provided additional evidence that the APOE4 genotype is a risk factor for amyloid-related imaging abnormalities, especially cerebral edema and effusion. These findings are consistent with those from other clinical trials of β-amyloid-targeting monoclonal antibodies in patients with Alzheimer disease. Breakdown of the blood-brain barrier may result in increased drug entry into the central nervous system that could have important safety implications because adverse events are generally dose-dependent. They would be grateful if Dr Sims and colleagues could discuss any data or insights they may have on the possible role of higher CSF donanemab levels in the increased risk for amyloid-related imaging abnormalities associated with the APOE ε4 genotype.