Platform research for the development of disease–modifying therapies for Alzheimer disease : J–ADNI and J–TRC

Abstract

A number of disease–modifying therapies (DMT) against Alzheimer disease (AD) are currently being tested in clinical trials, some of which met the clinical endpoints in registration–level trials like Clarity for lecanemab, which recently got accelerated approval in the United States, whereas others, especially those conducted in dementia stages, have failed, underscoring the needs for early intervention and biomarkers. To establish imaging and fluid biomarkers that surrogate the clinical and pathophysiological progression of AD, longitudinal observational studies as represented by AD Neuroimaging Initiative (ADNI) in US, as well as the Japanese ADNI, has been conducted, which contributed greatly towards the goal of very early treatment at the prodromal and preclinical AD stages by delineating the early natural course of AD. It has been demonstrated that the clinical and biomarker profiles of prodromal AD in J–ADNI were remarkably similar to those in North American ADNI, supporting the harmonization of global clinical trials. Furthermore, secondary prevention trials in preclinical AD, i.e., anti–Aβ therapies in asymptomatic, amyloid positive elderly individuals (the A4 study), as well as projects to establish trial ready cohorts (TRC) of preclinical and prodromal AD, are being conducted in US and Japan. J–TRC is comprised of a webstudy and an on–site study, recruiting ∼13000 and ∼528 participants, respectively. These clinical activities, accelerated by the development and implementation of biomarkers, will pave the way toward the development of very early treatment of AD.