Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer's brain tissue

The formation of A beta amyloid fibrils is a neuropathological hallmark of Alzheimer's disease and cerebral amyloid angiopathy. However, the structure of A beta amyloid fibrils from brain tissue is poorly understood. Here we report the purification of A beta amyloid fibrils from meningeal Alzheimer's brain tissue and their structural analysis with cryo-electron microscopy. We show that these fibrils are polymorphic but consist of similarly structured protofilaments. Brain derived A beta amyloid fibrils are right-hand twisted and their peptide fold differs sharply from previously analyzed A beta fibrils that were formed in vitro. These data underscore the importance to use patient-derived amyloid fibrils when investigating the structural basis of the disease.