Polymorphism at codon 174 of the prion-like protein gene is not associated with sporadic Alzheimer's disease

Alzheimer's disease (AD) and prion diseases are associated with the occurrence of protein aggregates called amyloid fibrils, containing the amyloid-P peptide in AD, and a modified form (PrPSc) of the normal cellular prion protein (PrPc) in prion diseases. PrPc is encoded by the prion protein gene, and a common polymorphism at codon 129 of this gene is a determinant of susceptibility to acquired and sporadic prion diseases but not for sporadic AD. A recently identified novel protein, named Doppel, shares biochemical and structural homology with PrPc. Preliminary evidence in a German population indicates that a polymorphism at codon 174 of the prion-like protein (PRND) gene encoding for Doppel protein is a predisposing factor for both prion diseases and sporadic AD. A case-control study utilizing a clinically well-defined group of 283 sporadic AD patients and 288 control subjects was performed to test this association. The current study does not demonstrate any significant difference in T174M PRND genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that the PRND gene is causally related to AD. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.