Optics

Physics

Biophysics

Pathology

Neuroscience

P3 peptide

Biochemistry of Alzheimer's disease

Chemistry

Fibril

Amyloid (mycology)

Cerebral amyloid angiopathy

Disease

Peptide

Dementia

Brain tissue

Amyloid fibril

Amyloid β

Amyloid precursor protein

Alzheimer's disease

Biochemistry

Medicine

Biology

Electron microscope

Nature Communications

The formation of Aβ amyloid fibrils is a neuropathological hallmark of Alzheimer’s disease and cerebral amyloid angiopathy. However, the structure of Aβ amyloid fibrils from brain tissue is poorly understood. Here we report the purification of Aβ 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 Aβ amyloid fibrils are right-hand twisted and their peptide fold differs sharply from previously analyzed Aβ 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.

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