title: A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease.
abstract: Cathepsin D (catD) is an intracellular acid protease possibly involved in Alzheimer's disease (AD)-related neurodegeneration through cleavage of amyloid precursor protein into amyloidogenic components. We studied whether an exonic polymorphism of the catD gene (C --> T [Ala --> Val] transition at position 224), which possibly influences pro-catD secretion and intracellular maturation of the enzyme, was associated with the risk for the development of AD in 127 demented patients and 184 controls. The catD*T allele was significantly overrepresented in demented patients (11.8%) compared with nondemented controls (4.9%). Carriers of the catD*T allele had a 3.1-fold increased risk for developing AD than noncarriers. Carriers of the apolipoprotein E (ApoE) epsilon4 allele (ApoE*4) had a 3.9-fold increased risk than non-carriers. The adjusted odds ratio for subjects with the ApoE*4 and the catD*T allele was 19.0 compared with subjects with neither of these two alleles. Our data confirm the results of a recently performed pilot study in an independent sample and suggest that the catD genotype is strongly associated with the risk for AD.
authors.affiliation: Department of Psychiatry, University of Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: M
authors.initials: M
authors.lastname: Bagli
authors.forename: A
authors.initials: A
authors.lastname: Kurz
authors.forename: J
authors.initials: J
authors.lastname: Kornhuber
authors.forename: H
authors.initials: H
authors.lastname: Förstl
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: J
authors.initials: J
authors.lastname: Pauls
authors.forename: N
authors.initials: N
authors.lastname: Lautenschlager
authors.forename: R
authors.initials: R
authors.lastname: Heun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics*; D002402:Cathepsin D / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D002402:Cathepsin D