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Science 31 October 2003:
Vol. 302. no. 5646, pp. 814 - 818
DOI: 10.1126/science.1087348
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Review

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 prion disorders (PrD) could not be more different. One-third of octogenarians succumb to AD, whereas Creutzfeldt-Jakob disease typically affects one individual in a million each year. However, these diseases have many common features impinging on the metabolism of neuronal membrane proteins: the amyloid precursor protein APP in the case of AD, and the cellular prion protein PrPC in PrD. APP begets the Aß peptide, whereas PrPC begets the malignant prion protein PrPSc. Both Aß and PrPSc are associated with disease, but we do not know what triggers their accumulation and neurotoxicity. A great deal has been learned, however, about protein folding, misfolding, and aggregation; an entirely new class of intramembrane proteases has been identified; and unsuspected roles for the immune system have been uncovered. There is reason to expect that prion research will profit from advances in the understanding 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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