β-Amyloid PET Signal Reduction in Prior ARIA-E Regions after Antiamyloid Therapy for Alzheimer Disease

Abstract

BACKGROUND AND PURPOSE: The relationship between regional brain edema caused by antiamyloid monoclonal antibodies (ARIA-E) and the degree of regional beta-amyloid (Aβ) PET signal reduction is unknown. We aimed at determining this relationship. MATERIALS AND METHODS: In patients with moderate or severe ARIA-E, we quantified changes in Aβ PET signal before and after ARIA-E resolution, comparing regions affected by ARIA-E with unaffected regions. RESULTS: In 4 of 5 patients treated with lecanemab or donanemab and who had moderate or severe ARIA-E, Aβ PET signal decreased significantly more in regions that had been involved with ARIA-E. CONCLUSIONS: Greater regional Aβ PET signal reduction in areas involved by ARIA-E may reflect enhanced local Aβ clearance, reduced tracer binding site availability, impaired glymphatic flow from immune complex deposition, or other mechanisms. The finding of greater regional Aβ PET signal reduction in ARIA-E regions refines the characterization of ARIA-E and raises the possibility that its occurrence may have beneficial as well as adverse implications.