Barbara Mroczko1, Magdalena Groblewska2, Marzena Zboch3, Agnieszka Kulczyńska4, Olga M Koper4, Maciej Szmitkowski5, Johannes Kornhuber6, Piotr Lewczuk6. 1. Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland Department of Biochemical Diagnostics, University Hospital in Białystok, Białystok, Poland. 2. Department of Biochemical Diagnostics, University Hospital in Białystok, Białystok, Poland. 3. Research-Scientific-Didactic Centre of Dementia-Related Diseases, Wrocław Medical University, Ścinawa, Poland. 4. Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland. 5. Department of Biochemical Diagnostics, University Hospital in Białystok, Białystok, Poland Department of Biochemical Diagnostics, Medical University of Białystok, Białystok, Poland. 6. Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Abstract
BACKGROUND: A growing body of evidence shows the involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in neurodegeneration processes, but reports of their concentrations in the cerebrospinal fluid (CSF) are inconsistent. OBJECTIVE: Therefore, the aim of our study was to evaluate the CSF concentrations of MMP-2, MMP-3, MMP-9, and their inhibitors (TIMP-1 and TIMP-2) in carefully selected groups of patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented controls, whose clinical and neuropsychological diagnoses were confirmed by the corresponding CSF biomarkers of neurochemical dementia diagnostics: decreased concentrations of Aβ1-42 and/or Aβ42/40 ratio, and increased concentrations of Tau and pTau181 proteins. METHODS: The study included 33 AD patients, 15 subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF concentrations of MMPs and TIMPs were determined with ELISAs. RESULTS: CSF concentrations of MMP-9 were significantly lower, and the concentrations of MMP-3 significantly higher in AD patients compared to the controls. Neither MMP-2 nor TIMPs showed significant changes among the groups investigated. CONCLUSION: Altered concentrations of two out of three MMPs investigated in this study suggest that this family of biomolecules may play a role in the AD pathophysiology. Further studies are needed to establish their potential diagnostic utility.
BACKGROUND: A growing body of evidence shows the involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in neurodegeneration processes, but reports of their concentrations in the cerebrospinal fluid (CSF) are inconsistent. OBJECTIVE: Therefore, the aim of our study was to evaluate the CSF concentrations of MMP-2, MMP-3, MMP-9, and their inhibitors (TIMP-1 and TIMP-2) in carefully selected groups of patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented controls, whose clinical and neuropsychological diagnoses were confirmed by the corresponding CSF biomarkers of neurochemical dementia diagnostics: decreased concentrations of Aβ1-42 and/or Aβ42/40 ratio, and increased concentrations of Tau and pTau181 proteins. METHODS: The study included 33 ADpatients, 15 subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF concentrations of MMPs and TIMPs were determined with ELISAs. RESULTS: CSF concentrations of MMP-9 were significantly lower, and the concentrations of MMP-3 significantly higher in ADpatients compared to the controls. Neither MMP-2 nor TIMPs showed significant changes among the groups investigated. CONCLUSION: Altered concentrations of two out of three MMPs investigated in this study suggest that this family of biomolecules may play a role in the AD pathophysiology. Further studies are needed to establish their potential diagnostic utility.
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