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 α-secretase that cleaves the β-amyloid precursor protein within its amyloidogenic Aβ domain. The gene encoding TIMP-1 (TIMP1) 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 TIMP1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP1 and one single nucleotide polymorphism in the 5′-untranslated region of TIMP1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP1 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 TIMP1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD.