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Games Played by Rogue Proteins in Prion Disorders and Alzheimer's Disease
Adriano Aguzzi1* and
Christian Haass2*
The incidence of Alzheimer's disease (AD) and that of priondisorders (PrD) could not be more different. One-third of octogenarianssuccumb to AD, whereas Creutzfeldt-Jakob disease typically affectsone individual in a million each year. However, these diseaseshave many common features impinging on the metabolism of neuronalmembrane proteins: the amyloid precursor protein APP in thecase of AD, and the cellular prion protein PrPC in PrD. APPbegets the Aß peptide, whereas PrPC begets the malignantprion protein PrPSc. Both Aß and PrPSc are associatedwith disease, but we do not know what triggers their accumulationand neurotoxicity. A great deal has been learned, however, aboutprotein folding, misfolding, and aggregation; an entirely newclass of intramembrane proteases has been identified; and unsuspectedroles for the immune system have been uncovered. There is reasonto expect that prion research will profit from advances in theunderstanding of AD, and vice versa.
1 Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland. 2 Department of Biochemistry, Adolf-Butenandt-Institute, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-University, Schillerstrasse 44, Munich, Germany.
* To whom correspondence should be addressed. E-mail: adriano{at}pathol.unizh.ch (A.A.); chaass{at}pbm.med.uni-muenchen.de (C.H.)
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