Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial.
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McCullough Austin, Chen Charles D, Gordon Brian A, Joseph-Mathurin Nelly, Jack Clifford R, Koeppe Robert, Hornbeck Russ, Koudelis Deborah, McKay Nicole S, Hobbs Diana A, Flores Shaney, Keefe Sarah J, Aggarwal Neelum T, Allegri Ricardo F, Berman Sarah B, Bird Thomas, Black Sandra E, Brooks William S, Chhatwal Jasmeer P, Day Gregory S, Farlow Martin R, Fox Nick C, Gauthier Serge, Honig Lawrence S, Hsiung Ging-Yuek, Jucker Mathias, Levin Johannes, Masellis Mario, Masters Colin, Mendez Patricio Chrem, Ringman John M, Snider B Joy, Salloway Stephen, Schofield Peter R, Shimada Hiroyuki, Suzuki Kazushi, van Dyck Christopher H, Klein Gregory, Clifford David B, Cruchaga Carlos, Hassenstab Jason, Li Yan, McDade Eric, Mills Susan, Morris John C, Perrin Richard J, Supnet-Bell Charlene, Wang Guoqiao, Xiong Chengjie, Bateman Randall J, Benzinger Tammie L S, DIAN‐TU Study Team
Аннотация
METHODS: In the DIAN-TU-001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [11C]-Pittsburgh compound-B (PiB) positron emission tomography (PET), [18F]-fluoro-2-deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI).
RESULTS: Gantenerumab significantly reduced PiB-PET uptake overall and in most regions and showed no changes in FDG-PET or MRI measures. Drug effects were associated with baseline PiB-PET uptake, and the largest effects occurred in medial regions.
DISCUSSION: Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB-PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design.
HIGHLIGHTS: Gantenerumab unevenly decreased Aβ burden as measured by PiB-PET across brain regions. The strongest decrease in PiB-PET uptake was in basal ganglia and medial frontal structures. Variable drug effect on Aβ was partly due to the amount of burden present before treatment. There was no regional effect on FDG-PET metabolism or MRI volumetrics after 4 years.