神経変性疾患を予防できる可能性

抄録

Therapeutic strategies for neurodegenerative diseases, such as Alzheimer disease (AD) and Parkinson disease (PD), have historically relied on symptomatic treatments that compensate for lost neuronal function but fail to halt irreversible degeneration. However, the elucidation of “proteinopathies”, which involve the aggregation of abnormal proteins like amyloid β and α–synuclein, has paved the way for disease–modifying therapies. The recent clinical implementation of anti–amyloid antibodies in AD marks a historic turning point, demonstrating that altering the disease trajectory is achievable. Given that intervention after the onset of clinical symptoms is often too late to prevent neuronal loss, research is rapidly shifting toward preemptive treatments during the preclinical or prodromal stages. AD research leads this change in paradigm with biological definitions based on biomarkers and novel prevention trials such as the AHEAD 3–45 study. In parallel with pharmacological approaches, multidomain lifestyle interventions are also gaining attention for their potential to enhance cognitive reserve. Following the progress in AD, PD research is evolving through large–scale observational cohorts and the introduction of the biological definition of Neuronal Synuclein Disease. In Japan, the authors are conducting the NaT–PROBE study to identify subjects at high risk for Lewy body disease using prodromal symptoms within a health checkup system. We also discuss the NaT–PROBEi study, a phase 2 pilot trial of zonisamide for prodromal subjects. Although the trial did not meet its primary endpoint, it provided critical insights into the need for subject stratification and long–term follow–up. This review outlines current prevention strategies in AD and their application to PD. We conclude that preventing neurodegenerative diseases is no longer a fantasy but a scientifically testable goal. Future success will depend on establishing personalized prevention strategies that optimize interventions based on individual genetic, pathological, and environmental risks.