Spectrum of amyloid-related imaging abnormalities associated with aducanumab treatment: a case series report
7 affiliations
- 1Banner Sun Health Research Institute, Banner Health, Sun City, AZ USA
- 2Mass General Brigham and Harvard Medical School, Boston, MA USA
- 3Biogen, 225 Binney Street, Cambridge, MA 02142 USA
- 4University of Southern California San Diego, San Diego, CA USA
- 5California Pacific Medical Center, Sutter Health, San Francisco, CA USA
- 6Clario, a part of Thermo Fisher Scientific, San Mateo, CA USA
- 7Clario, a part of Thermo Fisher Scientific, Lyon, France
Abstract
Background: Amyloid-related imaging abnormalities (ARIA) observed on magnetic resonance imaging (MRI) are known adverse events associated with beta-amyloid plaque-lowering monoclonal antibodies. A spectrum of radiographic and clinical presentations of ARIA have been observed. ARIA-E refer to vasogenic edema in the brain parenchyma and/or leptomeningeal/subpial sulcal effusion; ARIA-H refer to hemosiderin deposits including cerebral microhemorrhage and localized superficial siderosis. With clinical availability of anti-amyloid therapies for treatment of early clinical stage Alzheimer's disease, there is an important need for better awareness of ARIA and education among a diversity of clinicians and practice settings.
Methods: To illustrate the wide spectrum of ARIA, we present the clinical history, course, and MRI findings as well as summarize learnings and implications of 10 ARIA-E cases from the aducanumab phase 3 clinical trials EMERGE and ENGAGE (ClinicalTrials.gov identifiers NCT02484547 and NCT02477800). Monitoring and management of ARIA, including criteria and timing of MRI, and drug dosing actions were defined per protocol and based upon radiographic severity and clinical symptoms associated with ARIA. ARIA were detected by MRI performed at pre-specified intervals or in response to symptoms or for safety follow-up reasons.
Results: The majority of ARIA-E events were asymptomatic. Most ARIA-E events occurred within the first 8 aducanumab doses and generally resolved within 3–4 months whether dosing was continued (i.e. when ARIA-E was asymptomatic and of mild radiographic severity) or whether dosing was suspended or discontinued. Occasionally, ARIA-E were recurrent. ARIA-H (microhemorrhages and superficial siderosis) most commonly occurred concurrently with ARIA-E. However, ARIA-H without ARIA-E, termed isolated ARIA-H, occurred at a similar frequency in aducanumab- and placebo-treated groups. 10% of participants with ARIA in the 10 mg/kg group had accompanying symptoms. When present, symptoms of ARIA most frequently included headache, nausea, fatigue, dizziness, confusional state, and visual disturbance. Serious symptoms associated with ARIA were uncommon (occurring in 0.3% of the participants treated with the 10 mg/kg dose regimen).
Conclusions: These illustrative cases provide learnings into the nature and factors associated with ARIA that can increase knowledge for clinicians and trialists regarding the varied radiographic and clinical presentations and evolution of ARIA.
Trial registration: Clinical Trials NCT02484547, registered June 18, 2015, https://clinicaltrials.gov/study/NCT02484547.
Clinical Trials NCT02477800, registered June 18, 2015, https://clinicaltrials.gov/study/NCT02477800.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12883-026-05097-9.
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BibTeX
@article{atri2026spectrum,
title = {{Spectrum of amyloid-related imaging abnormalities associated with aducanumab treatment: a case series report}},
author = {Alireza Atri and Gioacchino G. Curiale and Paul Aisen and Jerome Barakos and Derk Purcell and Luc Bracoud and Samantha Budd Haeberlein and Christina Grassi and Richard Hughes and Karen Smirnakis},
journal = {BMC Neurology},
year = {2026},
month = jul,
doi = {10.1186/s12883-026-05097-9},
url = {https://doi.org/10.1186/s12883-026-05097-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Spectrum of amyloid-related imaging abnormalities associated with aducanumab treatment: a case series report
AU - Alireza Atri
AU - Gioacchino G. Curiale
AU - Paul Aisen
AU - Jerome Barakos
AU - Derk Purcell
AU - Luc Bracoud
AU - Samantha Budd Haeberlein
AU - Christina Grassi
AU - Richard Hughes
AU - Karen Smirnakis
PY - 2026
DA - 2026/07/30
JO - BMC Neurology
DO - 10.1186/s12883-026-05097-9
UR - https://doi.org/10.1186/s12883-026-05097-9
AB - Background: Amyloid-related imaging abnormalities (ARIA) observed on magnetic resonance imaging (MRI) are known adverse events associated with beta-amyloid plaque-lowering monoclonal antibodies. A spectrum of radiographic and clinical presentations of ARIA have been observed. ARIA-E refer to vasogenic edema in the brain parenchyma and/or leptomeningeal/subpial sulcal effusion; ARIA-H refer to hemosiderin deposits including cerebral microhemorrhage and localized superficial siderosis. With clinical availability of anti-amyloid therapies for treatment of early clinical stage Alzheimer's disease, there is an important need for better awareness of ARIA and education among a diversity of clinicians and practice settings. Methods: To illustrate the wide spectrum of ARIA, we present the clinical history, course, and MRI findings as well as summarize learnings and implications of 10 ARIA-E cases from the aducanumab phase 3 clinical trials EMERGE and ENGAGE (ClinicalTrials.gov identifiers NCT02484547 and NCT02477800). Monitoring and management of ARIA, including criteria and timing of MRI, and drug dosing actions were defined per protocol and based upon radiographic severity and clinical symptoms associated with ARIA. ARIA were detected by MRI performed at pre-specified intervals or in response to symptoms or for safety follow-up reasons. Results: The majority of ARIA-E events were asymptomatic. Most ARIA-E events occurred within the first 8 aducanumab doses and generally resolved within 3–4 months whether dosing was continued (i.e. when ARIA-E was asymptomatic and of mild radiographic severity) or whether dosing was suspended or discontinued. Occasionally, ARIA-E were recurrent. ARIA-H (microhemorrhages and superficial siderosis) most commonly occurred concurrently with ARIA-E. However, ARIA-H without ARIA-E, termed isolated ARIA-H, occurred at a similar frequency in aducanumab- and placebo-treated groups. 10% of participants with ARIA in the 10 mg/kg group had accompanying symptoms. When present, symptoms of ARIA most frequently included headache, nausea, fatigue, dizziness, confusional state, and visual disturbance. Serious symptoms associated with ARIA were uncommon (occurring in 0.3% of the participants treated with the 10 mg/kg dose regimen). Conclusions: These illustrative cases provide learnings into the nature and factors associated with ARIA that can increase knowledge for clinicians and trialists regarding the varied radiographic and clinical presentations and evolution of ARIA. Trial registration: Clinical Trials NCT02484547, registered June 18, 2015, https://clinicaltrials.gov/study/NCT02484547. Clinical Trials NCT02477800, registered June 18, 2015, https://clinicaltrials.gov/study/NCT02477800. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12883-026-05097-9.
SN - 1471-2377
ER -