Frontiers of drug development against Alzheimer disease : focusing on lecanemab

Abstract

The amyloid hypothesis, in which β–amyloid is considered to be the pathogenic protein of AD, has been widely supported by genetic and pathological evidence, and progress has been made in disease–modifying therapy (DMT) targeting the pathological mechanism of the disease. Passive immunization with humanized anti–Aβ antibodies has been pursued, and in 2023, lecanemab raised against protofibrillar form of Aβ achieved ∼27.1% reduction in the speed of clinical progression in early AD (mild cognitive impairment [MCI] to mild AD dementia), in an 18–month Phase III clinical trial, and was approved in the U.S. and Japan for clinical use. Problems in the practical use of lecanemab and anti–Aβ antibody drugs, as well as future perspectives in disease–modifying therapies, will be discussed.