Amyloid 42 fibrils

6 March 2009. The Aβ42 peptide may self-aggregate to form fibers with a structure profoundly different from those made of its less pathogenic cousin Aβ40. So suggests a cryoelectron microscopy (cryoEM) study—the first reported for Aβ1-42—in this week’s PNAS Early Edition. In contrast to structural studies of Aβ1-40 that have predicted a tight arrangement of protofilaments in mature fibers, the new model describes Aβ1-42 fibers as pairs of loosely connected protofilaments snaked around a hollow core. “There might be a weak link in this seemingly impenetrable molecule,” said neurologist Jin-Moo Lee of Washington University School of Medicine, St. Louis, Missouri, who led the new research. If fibrillar Aβ42 “is in fact a toxic species, then this is a potential site where we might disrupt the fibril,” Lee said. The authors and other scientists caution, though, that differences in growth conditions for the various Aβ species make it hard to directly compare structural studies of Aβ1-40 and Aβ1-42. The relevance of synthetic Aβ fibril structures—the kind used here—to Alzheimer disease also remains to be seen.