title: Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease.
abstract: The beta amyloid peptide derives from its precursor protein via proteolytic cleavage of yet unidentified proteases (beta- and gamma-secretases). Cathepsin D is an intracellular protease with in-vitro beta-secretase-like features. An exonic polymorphism of the cathepsin D gene (alanine to valine transition at position 224, exon 2) has been associated with altered enzyme function. We tested the hypothesis that this polymorphism is associated with an increased risk for Alzheimer's disease in 102 demented patients, 191 healthy subjects, and 160 depressed patients. There was a highly significant overrepresentation of the cathepsin D*T allele in demented patients (14.2%) compared to non-demented controls (6.7%, P = 0.0012). Carriers of the cathepsin D*T allele had a 2.4-fold increased risk for developing AD than non-carriers. Carriers of the apolipoprotein E epsilon 4 allele had a 4.1 -fold increased risk than non-carriers. The odds ratio for subjects with the apolipoprotein E epsilon 4 and the cathepsin D*T allele was 5.9. Our data suggest that the cathepsin D genotype is strongly associated with the risk for Alzheimer's disease.
authors.affiliation: Department of Psychiatry, University of Bonn, Germany. papassotiropoulos@uni-bonn.de
authors.forename: A
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: M
authors.initials: M
authors.lastname: Bagli
authors.forename: O
authors.initials: O
authors.lastname: Feder
authors.forename: F
authors.initials: F
authors.lastname: Jessen
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: M L
authors.initials: ML
authors.lastname: Rao
authors.forename: M
authors.initials: M
authors.lastname: Ludwig
authors.forename: S G
authors.initials: SG
authors.lastname: Schwab
authors.forename: R
authors.initials: R
authors.lastname: Heun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics*; D019943:Amino Acid Substitution; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002402:Cathepsin D / Q000235:genetics*; D003863:Depression / Q000235:genetics; D005091:Exons; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012016:Reference Values; D012307:Risk Factors; D014633:Valine
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002402:Cathepsin D; D014633:Valine; D000409:Alanine