Prion protein, notorious for causing the brain-wasting mad cow and Creutzfeldt-Jakob diseases, may also be a coconspirator in Alzheimer’s disease, a new study in mice suggests.
In mad cow and Creutzfeldt-Jakob diseases, misshapen prion proteins do the damage. But the new paper, appearing February 26 in Nature, offers evidence that the harmless version of the prion protein assists the amyloid-beta protein responsible for brain cell death in Alzheimer’s disease.
“It’s pretty sensational,” comments Adriano Aguzzi, a neuropathologist at the University of Zurich. “What’s tremendously electrifying is that prion protein may be a genetic sensor for extremely toxic, small concentrations of A-beta.”
A-beta proteins can travel alone or in groups in the brain. On their own, A-beta proteins are harmless. Massive, insoluble clumps of A-beta, known as plaques, are probably harmless, too, says study coauthor Stephen Strittmatter, a neuroscientist at Yale University. These plaques may be a gravestone marker of dead brain cells but are probably not the killer. Instead, smaller, soluble clumps of 50 to 100 A-beta proteins, known as oligomers, are the most likely suspect, Strittmatter says.
Earlier studies have shown that mice with A-beta oligomers can’t remember how to get through a maze as quickly as mice without A-beta oligomers. Such oligomers prevent cross-talk between certain brain cells in the hippocampus of mice, which helps explain the loss of learning and memory functions in Alzheimer’s disease.