Wollmer, M A; Papassotiropoulos, A; Streffer, J R; Grimaldi, L M E; Kapaki, E; Salani, G; Paraskevas, G P; Maddalena, A; de Quervain, D; Bieber, C; Umbricht, D; Lemke, U; Bosshardt, S; Degonda, N; Henke, K; Hegi, T; Jung, H H; Pasch, T; Hock, C; Nitsch, R M (2002). Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease. Psychiatric Genetics, 12(3):155-160.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine|
|DDC:||610 Medicine & health|
|Deposited On:||15 Sep 2011 08:43|
|Last Modified:||23 Nov 2012 15:40|
|Publisher:||Lippincott Wiliams & Wilkins|
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