Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial

Authors

Austin McCullough, Charles D Chen, Brian A Gordon, Nelly Joseph-Mathurin, Clifford R Jack, Robert Koeppe, Russ Hornbeck, Deborah Koudelis, Nicole S McKay, Diana A Hobbs, Shaney Flores, Sarah J Keefe, Neelum T Aggarwal, Ricardo F Allegri, Sarah B Berman, Thomas Bird, Sandra E Black, William S Brooks, Jasmeer P Chhatwal, Gregory S Day, Martin R Farlow, Nick C Fox, Serge Gauthier, Lawrence S Honig, Ging-Yuek Hsiung, Mathias Jucker, Johannes Levin, Mario Masellis, Colin Masters, Patricio Chrem Mendez, John M Ringman, B Joy Snider, Stephen Salloway, Peter R Schofield, Hiroyuki Shimada, Kazushi Suzuki, Christopher H van Dyck, Gregory Klein, David B Clifford, Carlos Cruchaga, Jason Hassenstab, Yan Li, Eric McDade, Susan Mills, John C Morris, Richard J Perrin, Charlene Supnet-Bell, Guoqiao Wang, Chengjie Xiong, Randall J Bateman, Tammie L S Benzinger, DIAN‐TU Study Team
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Abstract

Alzheimers Dement. 2025 Jul;21(7):e70347. doi: 10.1002/alz.70347.

ABSTRACT

INTRODUCTION: Monoclonal anti-amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD).

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.

PMID:40660741 | DOI:10.1002/alz.70347