Fiber Diffraction Data Indicate a Hollow Core for the Alzheimer's Aβ 3-Fold Symmetric Fibril

Amyloid β protein (Aβ), the principal component of the extracellular plaques found in the brains of patients with Alzheimer's disease, forms fibrils well suited to structural study by X-ray fiber diffraction. Fiber diffraction patterns from the 40-residue form Aβ(1–40) confirm a number of features of a 3-fold symmetric Aβ model from solidâstate NMR (ssNMR) but suggest that the fibrils have a hollow core not present in the original ssNMR models. Diffraction patterns calculated from a revised 3-fold hollow model with a more regular β-sheet structure are in much better agreement with the observed diffraction data than patterns calculated from the original ssNMR model. Refinement of a hollow-core model against ssNMR data led to a revised ssNMR model, similar to the fiber diffraction model. ⺠The Aβ peptide forms fibrils in plaques in the brains of patients with Alzheimer's disease. ⺠X-ray fiber diffraction data are complementary to ssNMR data. ⺠Combining fiber diffraction and ssNMR data leads to a new Aβ model. ⺠The 3-fold symmetric model has a hollow core. ⺠The hollow core may be significant for therapeutics and diagnosis.