Identifying Genetic Risk for Amyloid-Related Imaging Abnormalities
John Hardy1, Jonathan M Schott1
1From the Department of Neurodegenerative Disease (J.H., J.M.S.), UCL Institute of Neurology, London, UK.
Neurology
|January 2, 2024
Summary
Recent Alzheimer disease (AD) treatments using antiamyloid antibodies show modest clinical effects and clear amyloid-beta (Aβ) from the brain. However, these therapies carry the risk of antibody-related imaging abnormalities (ARIA), impacting their therapeutic use.
Area of Science:
- Neurology
- Immunotherapy
- Biomedical Imaging
Background:
- Three antiamyloid antibodies (aducanumab, lecanemab, donanemab) targeting amyloid-beta (Aβ) have shown success in Alzheimer disease (AD) trials.
- These therapies, used in early symptomatic AD stages, demonstrate modest clinical benefits and Aβ clearance, suggesting disease modification.
Discussion:
- A significant adverse event associated with these antiamyloid antibodies is antibody-related imaging abnormalities (ARIA).
- ARIA manifests as vasogenic edema/sulcal effusion (ARIA-E) or hemosiderin deposition from hemorrhage (ARIA-H), detected via MRI.
- The exact pathophysiology of ARIA is under investigation, potentially involving antibody-mediated plaque breakdown, Aβ deposition in cerebral vasculature, or inflammatory responses.
Key Insights:
- Antiamyloid antibodies offer a novel therapeutic strategy for Alzheimer disease by targeting Aβ plaques.
- Despite efficacy in Aβ clearance and potential disease modification, ARIA represents a critical safety concern.
- Understanding ARIA's mechanisms is crucial for optimizing the clinical application of these promising Alzheimer therapies.
Outlook:
- Further research into ARIA pathophysiology may lead to strategies for mitigating this adverse event.
- Continued investigation into the long-term clinical impact and safety profile of antiamyloid therapies is warranted.
- Development of improved diagnostic and monitoring tools for ARIA will be essential for patient management.
