The findings reported in the Journal of Neuroscience show that common cellular prion proteins – not the beta amyloid plaques themselves – are needed to produce the cognitive impairments associated with Alzheimer’s.
“Cellular prion protein is the essential mediator in Alzheimer’s that leads to memory dysfunction and reduced survival in mice,” said Stephen Strittmatter, the Vincent Coates Professor of Neurology, professor of neurobiology and senior author of the study.
Scientists have long debated whether the plaques associated with Alzheimer’s caused the devastating dementia that is the hallmark of the disease or were simply a side-effect of the disease process. The latter view has been supported by autopsy results that show the presence of Alzheimer-like plaques in brains of individuals who had suffered no memory loss or cognitive impairment.
A year ago, a team led by Strittmatter reported in the journal Nature that damage to neurons could be triggered when small soluble forms of amyloid beta peptide bind to a normally harmless cellular prion protein called PrP-C. In very rare cases the same cellular prion proteins can change shape and cause notorious diseases such as Creutzfeldt- Jacob disease or its variant. mad cow disease. This pathological event causes damage to neurons even in the absence of large insoluble amyloid plaques that are the hallmark of Alzheimer’s.
However, it is still unclear whether these prion proteins cause cognitive impairments associated with Alzheimer’s. In the Journal of Neuroscience study, the Yale team studied the memories of mice bred to have Alzheimer’s-like plaques. The team found these mice lacking PrP showed no detectable impairment in spatial learning in memory tests, even though their brains were riddled with beta amyloid plaques.
New Haven-based biotechnology company Axerion Therapeutics, Inc. has licensed the rights to develop the Yale research and plans to investigate potential clinical applications.
“Axerion is excited to begin translating this science into a therapeutic approach that will block the binding of harmful beta amyloid oligomers to these prion proteins and thereby reduce the devastating effects of Alzheimer’s Disease,” said Sylvia McBrinn, President and CEO of the company.
The project was funded by: National Institutes of Health, Alzheimer’s Association, and the Falk Medical Research Trust.
Other Yale authors were David Gimbel, Haakon Nygaard, Erin Coffey, Zachary Gimbel and Erik Gunther.
Citation: Journal of Neuroscience, May 5, 2010
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