Progressive Amyloid-Related Imaging Abnormalities After Discontinuation of Lecanemab in Early Alzheimer Disease in an APOE ε2/ε4 Carrier

Abstract

Background

Amyloid-related imaging abnormalities (ARIA) are the most relevant adverse events associated with anti-amyloid therapies in Alzheimer's disease.

Methods

We report a case of progressive ARIA after discontinuation of lecanemab in a patient with early-onset Alzheimer's disease carrying the rare APOE ε2/ε4 genotype.

Results

After two infusions, mild ARIA-edema (ARIA-E) and ARIA-hemorrhage (ARIA-H) were detected on routine MRI, prompting treatment interruption. Despite partial radiologic regression, follow-up MRI 8 weeks after discontinuation demonstrated marked progression with multifocal ARIA-H displaying as superficial siderosis, while the patient remained clinically asymptomatic. Corticosteroid treatment was initiated and lecanemab permanently discontinued.

Conclusion

This case highlights that severe ARIA may progress beyond active treatment exposure and emphasizes the importance of continued MRI surveillance even after therapy cessation. Furthermore, the APOE ε2/ε4 genotype may represent a distinct risk factor for cerebral amyloid angiopathy-related vascular fragility and hemorrhagic ARIA.