Resistance to cortical amyloid-beta associates with cognitive health in centenarians

BACKGROUND Amyloid-beta(Aβ)-plaques accumulate in non-demented individuals, particularly at advanced ages. The unclear association between Aβ-pathology and cognition in elderly raises the question whether Aβ-pathology should be considered a benign consequence of aging. METHODS Post-mortem brains of 95 centenarians and 27 Alzheimer’s disease(AD) patients were evaluated for Aβ-plaque distribution according to the Thal phase and quantitative Aβ-load in the neocortex. For centenarians, Aβ-pathology was correlated to APOE -genotype and performance on 12 cognitive tests administered shortly before death. FINDINGS While 35% of centenarians exhibited Aβ-loads similar to AD patients, cortical Aβ-load was limited in 65% of centenarians, some of which had the highest Thal phase. Cortical Aβ-load, as opposed to Thal phase, associated with APOE -genotype and cognitive performance in centenarians. DISCUSSION Despite increasing Aβ-accumulation in various brain regions with age, actual Aβ-loads remain low in cognitively healthy centenarians. Therefore, Aβ-pathology in the oldest-old may not be considered a benign consequence of aging.