Investigating Alzheimer’s Disease Resistance in Okinawan Centenarians’ Offspring: A Population Study in a Blue Zone

Abstract

Alzheimer’s disease (AD) is a neurodegenerative condition characterized by cognitive decline and the accumulation of amyloid-β plaques and neurofibrillary tangles in the brain. Although developing the disease becomes increasingly common as people age, centenarians — individuals who reach the age of 100 — have shown an unexpected resilience to AD, and these individuals are more prevalent in regions known as blue zones, where people experience exceptional longevity and health. This study focuses on the offspring of centenarians in one of these blue zones, Okinawa, Japan, to investigate what potential protective factors they may possess against AD. By screening this unique population using a questionnaire and the Mini-Mental State Examination (MMSE) and tracking AD pathology through advanced biomarker assays following the A/T/N criteria, A: Aβ40/42 ratio, T: phosphorylated tau (pT217-tau), and N: neurofilament light chain (NfL) levels, we aim to uncover genetic, environmental, or lifestyle-related factors that contribute to the decreased incidence of AD in these populations. This study seeks to identify key factors contributing to their resilience by comparing the results of centenarian offspring with age-matched non-centenarians. The spouses of these offspring of centenarians will also be included in the study, acting as a control group of individuals who are likely to share many of the lifestyle and environmental factors with the centenarian offspring but with different genetics. These findings could provide valuable insights for the future development of public health strategies and approaches to mitigate AD risk in the broader population.