(597a) Seeded Growth of Beta-Amyloid Fibrils From Alzheimer's Brain–Derived Fibrils Produces a Distinct Fibril Structure

Recent solid state NMR structural investigations of amyloid fibrils of the Alzheimer's β-amyloid peptide (Aβ) have revealed structures that are highly sensitive to environmental conditions during self-assembly (Paravastu, A.K., Leampan, R.D., Tycko, R., et. al. PNAS 105, 18349 (2008).). These results have raised questions on amyloid fibril structures formed in physiological environments. Using amyloid fibrils purified from the brains of deceased Alzheimer's patients, we have demonstrated that brain amyloid can seed the growth of synthetic Aβ amyloid fibrils (Paravastu, A.K., Meredith, S.C., Tycko, R., et. al. PNAS 106, 7443 (2009).). Resultant fibrils most likely represent disease-relevant amyloid fibril structures. Solid state NMR revealed identical structures from fibrils seeded from the brains of two different Alzheimer's patients. Furthermore, the predominant brain seeded fibrils differ structurally from those of well characterized synthetic Aβ fibrils. These results suggest the existence of a unique pathological microenvironment and demonstrate the feasibility of structural analysis of in vivo amyloid fibril deposits.