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Apr 02, 2009
 |  BC Innovations  |  Cover Story

New PrPetrator in AD

Yale University researchers have uncovered a surprising link between Alzheimer's disease and the prion protein that has been linked to mad cow disease and the related human condition, Creutzfeldt-Jakob disease.

The team has reported that prion protein (PRNP; PrP), which itself forms aggregates in prion diseases like Creutzfeldt-Jakob disease (CJD), is one of the main cellular receptors for oligomeric b-amyloid (Ab), the toxic misfolded protein behind AD.1 Targeting the interaction between Ab and PrP could thus be a new tack against AD.

Ab is a fragment of the amyloid-b (A4) precursor protein (APP), a neuronal surface protein, and forms the hallmark amyloid aggregates that clog the brains of AD patients. However, and despite numerous theories about how the oligomers trigger neuron death, the direct molecular target of Ab had, until now, been a mystery.

The Yale study in Naturenow offers strong in vitro evidence for PrP as a specific cellular Ab oligomer receptor.

"The mechanism by which the production of Ab makes neurons sick has been a black box," said Stephen Strittmatter, professor of neurology at Yale School of Medicine and lead author on the paper. "In this study we set out to understand how a certain form of Ab associated with disease, the oligomeric form, can interact with neurons and trigger the toxic cascade of the disease process. We identified PrP as the surface protein needed for Ab to disrupt functions of neurons in a dish."

The findings suggest that the two proteins activate a neurodegenerative disease signaling pathway common to both AD and CJD. The results further indicate that mAbs targeting PrP could be useful in treating AD. That could be good news for Prionics AG, a veterinary diagnostics company that has developed a range...

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