Centenarians maintain cognition by resisting amyloid-β or decoupling it from tau propagation

Researchers examined 112 centenarians to understand how they maintain cognitive abilities and resist Alzheimer's disease. They found that amyloid-beta pathology was associated with increased p-tau burden in the parahippocampal region and lower cognitive performance. However, most centenarians maintained high cognitive performance until death through two distinct mechanisms: 44 percent were resistant to amyloid-beta accumulation, while 28 percent had substantial amyloid-beta pathology but resisted p-tau propagation. The research suggests the existence of natural resilience mechanisms that decouple amyloid-beta pathology from tau progression. Both mechanisms could offer new therapeutic approaches: either preventing amyloid-beta accumulation or limiting p-tau propagation after it has already emerged.