title: Analysis of matrix metallo-proteases and the plasminogen system in mild cognitive impairment and Alzheimer's disease cerebrospinal fluid.
abstract: The expression of matrix metallo-proteases (MMP-2, MMP-3, MMP-7, and MMP-9), plasminogen and their regulators (TIMP-1, tissue plasminogen activator and neuroserpin) was investigated in cerebrospinal fluid (CSF) from subjective cognitive impairment (SCI) subjects, mild cognitive impairment (MCI), and Alzheimer's disease (AD) cases. ELISA analysis revealed a significant increase in MMP-3 protein levels in CSF from AD subjects, compared to age-matched SCI and MCI cases. No significant differences in MMP-2 and MMP-9 protein levels were detected between the three groups. MMP-7 was undetectable in all three groups. MCI individuals exhibited increased levels of the metallo-protease inhibitor TIMP-1 in CSF as well as higher plasminogen and neuroserpin expression, compared to SCI subjects. Levels of tissue plasminogen activator (tPA) were significantly reduced in AD CSF. Correlation analysis revealed a significant positive association between MMP-3, p-tau, and total-tau levels. Conversely, there was a significant negative correlation between this protease and Mini-Mental State Examination (MMSE) scores. tPA positively correlated with amyloid-β levels in CSF and with MMSE scores. Our results suggest that MMP-3 and tPA, in combination with current amyloid-β and tau biomarkers, may have potential as surrogate indicators of an ongoing AD pathology.
authors: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors: Cecilia E
authors: CE
authors: Hanzel
authors: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
authors: M Florencia
authors: MF
authors: Iulita
authors: Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors: Helga
authors: H
authors: Eyjolfsdottir
authors: Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
authors: Erik
authors: E
authors: Hjorth
authors: Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
authors: Marianne
authors: M
authors: Schultzberg
authors: Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors: Maria
authors: M
authors: Eriksdotter
authors: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors: A Claudio
authors: AC
authors: Cuello
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis* / Q000134:cerebrospinal fluid*; D008609:Mental Status Schedule; D008875:Middle Aged; D009479:Neuropeptides; D010958:Plasminogen / Q000032:analysis* / Q000134:cerebrospinal fluid*; D015843:Serpins; D010959:Tissue Plasminogen Activator; D000097522:Neuroserpin
chemical_list: D020782:Matrix Metalloproteinases; D009479:Neuropeptides; D010958:Plasminogen; D015843:Serpins; D010959:Tissue Plasminogen Activator; D000097522:Neuroserpin
keywords: Alzheimer's disease; biomarkers; metallo-proteases; neuroserpin; plasminogen