title: Cerebrospinal fluid levels of beta-amyloid(42) in patients with Alzheimer's disease are related to the exon 2 polymorphism of the cathepsin D gene.
abstract: The intracellular aspartyl protease cathepsin D (catD) is involved in such Alzheimer's disease (AD)-related processes as the activation of the endosomal/lysosomal system and the cleavage of the amyloid precursor protein into amyloidogenic components, which may initiate neurodegeneration. A non-synonymous polymorphism (exon 2, C to T exchange leading to ala-->val substitution) of the gene encoding catD (CTSD) was previously associated with AD, in that the T allele increased the risk for AD. To investigate whether the T allele is associated with disease-related traits, we measured the concentration of the amyloid beta-peptide 1-42 (Abeta(42)) and 1-40 (Abeta(40)) in patients and control subjects. The T allele of the CTSD genotype was associated with a 50% decrease in Abeta(42) levels in the cerebrospinal fluid. Thus, we demonstrate a significant impact of the CTSD genotype on Abeta(42) levels in the cerebrospinal fluid of AD patients and underpin the importance of the validation of susceptibility genes by examining their potential pathophysiological relevance.
authors.affiliation: Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: Huw D
authors.initials: HD
authors.lastname: Lewis
authors.forename: Metin
authors.initials: M
authors.lastname: Bagli
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Ursula
authors.initials: U
authors.lastname: Ptok
authors.forename: Andrea
authors.initials: A
authors.lastname: Schulte
authors.forename: Mark S
authors.initials: MS
authors.lastname: Shearman
authors.forename: Reinhard
authors.initials: R
authors.lastname: Heun
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002402:Cathepsin D / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011110:Polymorphism, Genetic
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D002402:Cathepsin D