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Lecanemab and donanemab have received full U.S. Food and Drug Administration (FDA) approval, and subsequently, lecanemab has been approved by the Korean FDA and it has recently entered commercial use in Korea. This has increased interest in anti-amyloid immunotherapy for Alzheimer's disease. Anti-amyloid immunotherapy has shown potential to modify the progression of the disease by specifically binding to amyloid β, a key pathological product in Alzheimer's disease, and eliminating accumulated amyloid plaques in the brain. However, this treatment can be accompanied by a side-effect, amyloid-related imaging abnormalities (ARIA), which requires periodic monitoring by MRI. It is crucial to detect ARIA and accurately assess the severity by radiology. The role of the radiologist is important in this context, requiring proficiency in basic knowledge of ARIA, and in diagnosing/evaluating ARIA. This review aims to comprehensively cover aspects of ARIA, including its definition, pathophysiology, incidence, risk factors, assessment of severity by radiology, differential diagnosis, and management.
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http://dx.doi.org/10.3348/jksr.2024.0140 | DOI Listing |
Eur Radiol
September 2025
Department of Radiology and Imaging Sciences, University of Utah, 30N Mario Capecchi Drive, 2 South, Salt Lake City, UT, USA.
Alzheimer disease (AD) is the most common dementing disorder, affecting 55 million people worldwide. Brain MRI plays an integral role in the diagnostic evaluation of patients with cognitive symptoms. When interpreting brain MRI for cognitive impairment, radiologists should assess the following four key features: (1) white matter ischemic burden, (2) structural changes to suggest normal pressure hydrocephalus, (3) locoregional pattern of brain atrophy, and (4) presence of microhemorrhage or superficial siderosis, particularly for determining eligibility for anti-amyloid monoclonal antibody (MAB) treatment when appropriate.
View Article and Find Full Text PDFAlzheimers Dement
August 2025
Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, London, UK.
Introduction: Cerebral microhemorrhages (CMHs) and superficial siderosis (SS) are relatively common side effects of anti-amyloid immunotherapies, termed amyloid-related imaging abnormalities (ARIA-H). They are also observed in treatment-naïve older adults. This study explored relationships with modifiable and non-modifiable risk factors.
View Article and Find Full Text PDFMol Neurodegener
August 2025
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Anti-amyloid β-peptide (Aβ) immunotherapy was developed to reduce amyloid plaque pathology and slow cognitive decline during progression of Alzheimer's disease. Efficient amyloid clearance has been proven in clinical trials testing anti-Aβ antibodies, by their impact on cognitive endpoints correlating with the extent of amyloid removal. However, treatment is associated with adverse side effects, such as oedema and haemorrhages, which are potentially linked to the induced immune response.
View Article and Find Full Text PDFScience
August 2025
Denali Therapeutics, Inc., South San Francisco, CA, USA.
Amyloid-related imaging abnormalities (ARIA), side effects of anti-amyloid drugs seen in magnetic resonance imaging of the brain, are a major safety concern in patients with Alzheimer's disease. We developed an antibody transport vehicle (ATV) targeting transferrin receptor (TfR) for brain delivery of anti-amyloid-β protein (anti-Aβ) using asymmetrical Fc mutations (ATV) that mitigates TfR-related liabilities and retains effector function when bound to Aβ. Administration of ATV:Aβ in mice exhibited broad brain distribution and enhanced parenchymal plaque target engagement.
View Article and Find Full Text PDFJ Alzheimers Dis
July 2025
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia.
BackgroundAnti-amyloid-β (Aβ) immunotherapies are emerging as treatments for Alzheimer's disease (AD).ObjectiveThis review examines the structure-activity relationships of anti-Aβ therapeutics tested in phase 3 trials.MethodsWe analyzed crystallographic data and molecular models to elucidate the Aβ binding mechanisms of donanemab, lecanemab, aducanumab, bapineuzumab, gantenerumab, solanezumab, and crenezumab.
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