medRxiv · Aug 30, 2022
Resilience and resistance to Alzheimer’s disease-associated neuropathological substrates in centenarians: an age-continuous perspective
By Zhang M, Ganz AB, Rohde SK et al.
Abstract INTRODUCTION With increasing age, neuropathology associated with Alzheimer’s disease (AD) accumulates in brains of cognitively healthy individuals: are they resilient or resistant against AD-associated neuropathologies? METHODS In 85 centenarian brains, we correlated NIA-Amyloid stages, Braak-NFT stages and CERAD-NP scores with cognitive performance determined close to death (MMSE). We assessed centenarian brains in context of 2,131 brains from AD patients, non-AD demented and non-demented individuals (age-range 16-100+ years). RESULTS With age, brains from non-demented individuals reached NIA-Amyloid and Braak-NFT stages as observed in AD patients, while CERAD-NP scores remained lower. In centenarians, NIA-Amyloid stages varied (22.4% had the highest stage 3), Braak-NFT stages rarely exceeded IV (5.9% had stage V), and CERAD-NP scores rarely exceeded 2 (4.7% had score 3); within these distributions, we observed no correlation with MMSE (NIA-Amyloid: P =0.60; Braak-NFT: P =0.08; CERAD-NP: P =0.16). DISCUSSION Cognitive health can be maintained despite the accumulation of high levels of AD-related neuropathological substrates.