Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease.
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.
Wollmer
M Axel
MA
Division of Psychiatry Research, University of Zurich, Switzerland. awollmer@bli.unizh.ch
Papassotiropoulos
Andreas
A
Streffer
Johannes R
JR
Grimaldi
Luigi M E
LM
Kapaki
Elisabeth
E
Salani
Giuliana
G
Paraskevas
George P
GP
Maddalena
Alessia
A
de Quervain
Dominique
D
Bieber
Claudia
C
Umbricht
Daniel
D
Lemke
Ulrike
U
Bosshardt
Simone
S
Degonda
Nadia
N
Henke
Katharina
K
Hegi
Thomas
T
Jung
Hans H
HH
Pasch
Thomas
T
Hock
Christoph
C
Nitsch
Roger M
RM
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*
D020121:5' Untranslated Regions; D019715:Tissue Inhibitor of Metalloproteinase-1; D004247:DNA