title: Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease.
abstract: Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD.
authors.affiliation: Division of Psychiatry Research, University of Zurich, Switzerland. awollmer@bli.unizh.ch
authors.forename: M Axel
authors.initials: MA
authors.lastname: Wollmer
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Streffer
authors.forename: Luigi M E
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kapaki
authors.forename: Giuliana
authors.initials: G
authors.lastname: Salani
authors.forename: George P
authors.initials: GP
authors.lastname: Paraskevas
authors.forename: Alessia
authors.initials: A
authors.lastname: Maddalena
authors.forename: Dominique
authors.initials: D
authors.lastname: de Quervain
authors.forename: Claudia
authors.initials: C
authors.lastname: Bieber
authors.forename: Daniel
authors.initials: D
authors.lastname: Umbricht
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lemke
authors.forename: Simone
authors.initials: S
authors.lastname: Bosshardt
authors.forename: Nadia
authors.initials: N
authors.lastname: Degonda
authors.forename: Katharina
authors.initials: K
authors.lastname: Henke
authors.forename: Thomas
authors.initials: T
authors.lastname: Hegi
authors.forename: Hans H
authors.initials: HH
authors.lastname: Jung
authors.forename: Thomas
authors.initials: T
authors.lastname: Pasch
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000134:cerebrospinal fluid* / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D019715:Tissue Inhibitor of Metalloproteinase-1; D004247:DNA