2025 Volume 42 Issue 3 Pages 249-254
In the development of anti amyloid β (Aβ) antibody therapy for Alzheimer disease patients, amyloid–related imaging abnormality (ARIA) is increasingly recognized as the major side effect. ARIA has been classified to ARIA–E (edema/effusion) and ARIA–H (microhemorrhage/hemosideros). In Japan lecanemab has been approved in 2023, and subsequently donanemab in 2024. The both antibodies bind aggregates of Aβ with varying affinity to some extent ; lecanemab preferrentially with protofibril, and donanemab with aggregated pyroglutamyl Aβ. For the early and sensitive detection of ARIA, optimal use guidelines for lecanemab and donanemab request regular examination with head MRI especially until 6 months, during which most ARIA cases are encountered. The risk of ARIA increases with APOE ε4 gene dosage, the severity of cerebral amyloid angiopathy (CAA) and dosage of antibodies. Therefore, appropriate use criteria in the US strongly recomended a pretest with APOE genotyping, whereas in Japan, it is not mandatory at present. The severity of CAA is also the risk of ARIA, which is prescribed as the number of cerebral microbleeds and cortical superficial siderosis. This review overviews an update of ARIA, including the pathophysiology and practical use recommendations for anti Aβ antibody therapy.
