TY  - JOUR
AU  - McCullough, Austin
AU  - Chen, Charles D
AU  - Gordon, Brian A
AU  - Joseph-Mathurin, Nelly
AU  - Jack, Clifford R
AU  - Koeppe, Robert
AU  - Hornbeck, Russ
AU  - Koudelis, Deborah
AU  - McKay, Nicole S
AU  - Hobbs, Diana A
AU  - Flores, Shaney
AU  - Keefe, Sarah J
AU  - Aggarwal, Neelum T
AU  - Allegri, Ricardo F
AU  - Berman, Sarah B
AU  - Bird, Thomas
AU  - Black, Sandra E
AU  - Brooks, William S
AU  - Chhatwal, Jasmeer P
AU  - Day, Gregory S
AU  - Farlow, Martin R
AU  - Fox, Nick C
AU  - Gauthier, Serge
AU  - Honig, Lawrence S
AU  - Hsiung, Ging-Yuek
AU  - Jucker, Mathias
AU  - Levin, Johannes
AU  - Masellis, Mario
AU  - Masters, Colin
AU  - Mendez, Patricio Chrem
AU  - Ringman, John M
AU  - Snider, B Joy
AU  - Salloway, Stephen
AU  - Schofield, Peter R
AU  - Shimada, Hiroyuki
AU  - Suzuki, Kazushi
AU  - van Dyck, Christopher H
AU  - Klein, Gregory
AU  - Clifford, David B
AU  - Cruchaga, Carlos
AU  - Hassenstab, Jason
AU  - Li, Yan
AU  - McDade, Eric
AU  - Mills, Susan
AU  - Morris, John C
AU  - Perrin, Richard J
AU  - Supnet-Bell, Charlene
AU  - Wang, Guoqiao
AU  - Xiong, Chengjie
AU  - Bateman, Randall J
AU  - Benzinger, Tammie L S
TI  - Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial.
JO  - Alzheimer's and dementia
VL  - 21
IS  - 7
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2025-00860
SP  - e70347
PY  - 2025
AB  - 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).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).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.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.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.
KW  - Humans
KW  - Alzheimer Disease: drug therapy
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: pathology
KW  - Positron-Emission Tomography
KW  - Male
KW  - Female
KW  - Magnetic Resonance Imaging
KW  - Brain: diagnostic imaging
KW  - Brain: drug effects
KW  - Brain: pathology
KW  - Brain: metabolism
KW  - Antibodies, Monoclonal, Humanized: therapeutic use
KW  - Antibodies, Monoclonal, Humanized: pharmacology
KW  - Neuroimaging
KW  - Middle Aged
KW  - Biomarkers: metabolism
KW  - Thiazoles
KW  - Fluorodeoxyglucose F18
KW  - Aniline Compounds
KW  - Aged
KW  - Amyloid beta-Peptides: metabolism
KW  - DIAN‐TU (Other)
KW  - FDG‐PET (Other)
KW  - MRI measures (Other)
KW  - PET (Other)
KW  - amyloid targeted monoclonal antibody (Other)
KW  - autosomal dominant Alzheimer's disease (ADAD) (Other)
KW  - dominantly inherited Alzheimer's disease (DIAD) (Other)
KW  - gantenerumab (Other)
KW  - imaging outcomes (Other)
KW  - regional PiB‐PET uptake (Other)
KW  - regional variability (Other)
KW  - Antibodies, Monoclonal, Humanized (NLM Chemicals)
KW  - gantenerumab (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - Thiazoles (NLM Chemicals)
KW  - Fluorodeoxyglucose F18 (NLM Chemicals)
KW  - Aniline Compounds (NLM Chemicals)
KW  - 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40660741
DO  - DOI:10.1002/alz.70347
UR  - https://pub.dzne.de/record/279900
ER  -