Structural diversity of ex vivo amyloid fibrils studied by cryo-electron microscopy

Cryo-electron microscopy studies are presented on amyloid fibrils isolated from amyloidotic organs of two patients with different forms of hereditary non-neuropathic systemic amyloidosis, caused, respectively, by Leu60Arg apo lipoprotein Al and Asp67His lysozyme. Although ex vivo amyloid fibrils were thought to be more uniform in structure than those assembled in vitro, our findings show that these fibrils are also quite variable in structure. Str uctural disorder and variability of the fibrils have precluded three-dimens ional reconstruction, but averaged cryo-electron microscopy images suggest models for protofilament packing in the lysozyme fibrils. We conclude that ex vivo amyloid fibrils, although variable, assemble as characteristic stru ctures according to the identity of the precursor protein. (C) 2001 Academi c Press.