In 2009, a team from the lab of Stephen M. Strittmatter, M.D., Ph.D., reported in Nature that small amyloid beta (A-β) molecules— which aggregate to form the plaques seen in Alzheimer’s disease (AD) patients’ brains—bind to neurons expressing cellular prion protein (PrPc), a ubiquitous protein in the normal brain. When A-β bound to PrPc, neural processes believed to underlie memory formation were compromised, leading the researchers to hypothesize that PrPc binding of A-β is a key early player in the cognitive decline of AD.
In the May 5 issue of the Journal of Neuroscience, Strittmatter and colleagues present more evidence. Studying a mouse model of AD, the group found that mice bred to lack PrPc showed no impairment in spatial learning and memory—even though their brains were riddled with A-β plaques. Mice expressing PrPc showed marked memory deficits and died significantly earlier than their counterparts.
“Cellular prion protein is the essential mediator that leads to Alzheimer’s-like memory dysfunction and reduced survival in these model mice,” says Strittmatter, the Vincent Coates Professor of Neurology and co-director of the Program in Cellular Neuroscience, Neurodegeneration, and Repair.