title: The cathepsin D rs17571 polymorphism: effects on CSF tau concentrations in Alzheimer disease.
abstract: The lysosomal protease cathepsin D (CtsD, EC 3.4.23.5; gene, CTSD) has been associated with Alzheimer disease (AD) due to its cerebral expression being increased early in the course of AD; additionally, a CTSD exon 2 polymorphism (rs17571; NT_009237.17:g.569834T>C) may confer risk to AD. Functionally, it may be implicated in amyloid precursor protein (APP) processing and tau protein degradation. The objective of this study was to determine whether the CTSD exon 2 polymorphism affects cerebrospinal fluid (CSF), concentrations of beta-amyloid (Abeta42) and tau in two independent samples from Germany (n=73) and Sweden (n=66). Patients carrying the CTSD rs17571-T allele had significantly decreased CSF levels of tau (Munich, p=0.003; Swedish, p=0.029; combined sample, p<0.001), whereas no significant effect was observed on Abeta42 concentrations. Likewise, no significant impact was observed on Mini Mental State Examination (MMSE) scores. The data of both independent samples suggest that the CTSD rs17571 polymorphism does not affect APP processing but shows significant effects on tau processing. The result may corroborate the implication of the lysosomal system in the pathogenesis of AD and is of particular importance if CSF tau is used as a diagnostic biomarker.
authors.affiliation: Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany. m.riemenschneider@lrz.tu-muenchen.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Riemenschneider
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Prince
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
authors.forename: Hans
authors.initials: H
authors.lastname: Förstl
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D002402:Cathepsin D / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D002402:Cathepsin D