Journal Article DZNE-2025-00860

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

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2025
Wiley Hoboken, NJ

Alzheimer's and dementia 21(7), e70347 () [10.1002/alz.70347]

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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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: drug therapy (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Positron-Emission Tomography (MeSH) ; Male (MeSH) ; Female (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: drug effects (MeSH) ; Brain: pathology (MeSH) ; Brain: metabolism (MeSH) ; Antibodies, Monoclonal, Humanized: therapeutic use (MeSH) ; Antibodies, Monoclonal, Humanized: pharmacology (MeSH) ; Neuroimaging (MeSH) ; Middle Aged (MeSH) ; Biomarkers: metabolism (MeSH) ; Thiazoles (MeSH) ; Fluorodeoxyglucose F18 (MeSH) ; Aniline Compounds (MeSH) ; Aged (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; DIAN‐TU ; FDG‐PET ; MRI measures ; PET ; amyloid targeted monoclonal antibody ; autosomal dominant Alzheimer's disease (ADAD) ; dominantly inherited Alzheimer's disease (DIAD) ; gantenerumab ; imaging outcomes ; regional PiB‐PET uptake ; regional variability ; Antibodies, Monoclonal, Humanized ; gantenerumab ; Biomarkers ; Thiazoles ; Fluorodeoxyglucose F18 ; Aniline Compounds ; 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole ; Amyloid beta-Peptides

Classification:

Contributing Institute(s):
  1. Cell Biology of Neurological Diseases (AG Jucker)
  2. Clinical Neurodegeneration (AG Levin)
  3. Clinical Research (Munich) (Clinical Research (Munich))
Research Program(s):
  1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
  2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
Experiment(s):
  1. Longitudinal Study on Dominantly Inherited Alzheimer's Disease

Appears in the scientific report 2025
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Medline ; Creative Commons Attribution-NonCommercial CC BY-NC 4.0 ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Institute Collections > M DZNE > M DZNE-Clinical Research (Munich)
Document types > Articles > Journal Article
Institute Collections > TÜ DZNE > TÜ DZNE-AG Jucker
Institute Collections > M DZNE > M DZNE-AG Levin
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 Record created 2025-07-17, last modified 2025-08-24