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@ARTICLE{McCullough:279900,
author = {McCullough, Austin and Chen, Charles D and Gordon, Brian A
and Joseph-Mathurin, Nelly and Jack, Clifford R and Koeppe,
Robert and Hornbeck, Russ and Koudelis, Deborah and McKay,
Nicole S and Hobbs, Diana A and Flores, Shaney and Keefe,
Sarah J and Aggarwal, Neelum T and Allegri, Ricardo F and
Berman, Sarah B and Bird, Thomas and Black, Sandra E and
Brooks, William S and Chhatwal, Jasmeer P and Day, Gregory S
and Farlow, Martin R and Fox, Nick C and Gauthier, Serge and
Honig, Lawrence S and Hsiung, Ging-Yuek and Jucker, Mathias
and Levin, Johannes and Masellis, Mario and Masters, Colin
and Mendez, Patricio Chrem and Ringman, John M and Snider, B
Joy and Salloway, Stephen and Schofield, Peter R and
Shimada, Hiroyuki and Suzuki, Kazushi and van Dyck,
Christopher H and Klein, Gregory and Clifford, David B and
Cruchaga, Carlos and Hassenstab, Jason and Li, Yan and
McDade, Eric and Mills, Susan and Morris, John C and Perrin,
Richard J and Supnet-Bell, Charlene and Wang, Guoqiao and
Xiong, Chengjie and Bateman, Randall J and Benzinger, Tammie
L S},
collaboration = {Team, DIAN-TU Study},
title = {{R}egional effects of gantenerumab on neuroimaging
biomarkers in the {DIAN}-{TU}-001 trial.},
journal = {Alzheimer's and dementia},
volume = {21},
number = {7},
issn = {1552-5260},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DZNE-2025-00860},
pages = {e70347},
year = {2025},
abstract = {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.},
keywords = {Humans / Alzheimer Disease: drug therapy / Alzheimer
Disease: diagnostic imaging / Alzheimer Disease: genetics /
Alzheimer Disease: pathology / Positron-Emission Tomography
/ Male / Female / Magnetic Resonance Imaging / Brain:
diagnostic imaging / Brain: drug effects / Brain: pathology
/ Brain: metabolism / Antibodies, Monoclonal, Humanized:
therapeutic use / Antibodies, Monoclonal, Humanized:
pharmacology / Neuroimaging / Middle Aged / Biomarkers:
metabolism / Thiazoles / Fluorodeoxyglucose F18 / Aniline
Compounds / Aged / Amyloid beta-Peptides: metabolism /
DIAN‐TU (Other) / FDG‐PET (Other) / MRI measures (Other)
/ PET (Other) / amyloid targeted monoclonal antibody (Other)
/ autosomal dominant Alzheimer's disease (ADAD) (Other) /
dominantly inherited Alzheimer's disease (DIAD) (Other) /
gantenerumab (Other) / imaging outcomes (Other) / regional
PiB‐PET uptake (Other) / regional variability (Other) /
Antibodies, Monoclonal, Humanized (NLM Chemicals) /
gantenerumab (NLM Chemicals) / Biomarkers (NLM Chemicals) /
Thiazoles (NLM Chemicals) / Fluorodeoxyglucose F18 (NLM
Chemicals) / Aniline Compounds (NLM Chemicals) /
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (NLM
Chemicals) / Amyloid beta-Peptides (NLM Chemicals)},
cin = {AG Jucker / AG Levin / Clinical Research (Munich)},
ddc = {610},
cid = {I:(DE-2719)1210001 / I:(DE-2719)1111016 /
I:(DE-2719)1111015},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
experiment = {EXP:(DE-2719)DIAN-20090101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40660741},
doi = {10.1002/alz.70347},
url = {https://pub.dzne.de/record/279900},
}