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      Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases

      , , , , , ,
      Journal of the Neurological Sciences
      Elsevier BV

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          Abstract

          Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS). Increased expression of MMP-9 and TIMPs has been reported in postmortem AD and ALS brain tissue, as well as in ALS cerebrospinal fluid (CSF) and plasma. Although individual studies of MMP and TIMP expression in CSF have included AD and ALS samples, there are no studies comparing the expression of these proteins between neurodegenerative diseases. We measured the levels of matrix metalloproteinases (MMPs)-2 and -9 and the tissue inhibitor of MMPs (e.g. TIMP-1 and TIMP-2) in CSF samples from patients with Parkinson's Disease (PD), Huntington's Disease (HD), AD and ALS as compared to age-matched control patients. There was constitutive expression of the proform of gelatinase A (proMMP-2) on zymography gels in all CSF samples. Unexpectedly, there was an additional gelatinolytic band at 130 kDa of unknown etiology in the CSF samples of patients with PD (61% of patients studied), AD (61%), HD (25%) and ALS (39%). Levels of TIMP-1 were significantly elevated in CSF samples from all disease groups. TIMP-2 was significantly increased in CSF of AD and HD patients. MMP-2 levels did not differ significantly between groups. These findings show that TIMPs are elevated in the CSF of patients with neurodegenerative diseases suggesting a potential role of these endogenous inhibitors of matrix metalloproteinases in neurodegenerative diseases.

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          Author and article information

          Journal
          Journal of the Neurological Sciences
          Journal of the Neurological Sciences
          Elsevier BV
          0022510X
          March 2003
          March 2003
          : 207
          : 1-2
          : 71-76
          Article
          10.1016/S0022-510X(02)00398-2
          12614934
          9a5a7452-ea5a-4084-9e87-7cb577070926
          © 2003

          https://www.elsevier.com/tdm/userlicense/1.0/

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