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

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