Concentrations of matrix metalloproteinases and their tissue inhibitors in the cerebrospinal fluid of patients with Alzheimer's disease.
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.


CONCLUSIONS
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.
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland Department of Biochemical Diagnostics, University Hospital in Białystok, Białystok, Poland.
Barbara
B
Mroczko
Department of Biochemical Diagnostics, University Hospital in Białystok, Białystok, Poland.
Magdalena
M
Groblewska
Research-Scientific-Didactic Centre of Dementia-Related Diseases, Wrocław Medical University, Ścinawa, Poland.
Marzena
M
Zboch
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
Agnieszka
A
Kulczyńska
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
Olga M
OM
Koper
Department of Biochemical Diagnostics, University Hospital in Białystok, Białystok, Poland Department of Biochemical Diagnostics, Medical University of Białystok, Białystok, Poland.
Maciej
M
Szmitkowski
Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Johannes
J
Kornhuber
Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Piotr
P
Lewczuk
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000134:cerebrospinal fluid*; D020782:Matrix Metalloproteinases / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D013129:Spinal Puncture; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D061965:Matrix Metalloproteinase Inhibitors; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D020782:Matrix Metalloproteinases
Alzheimer's disease; biomarkers; cerebrospinal fluid; matrix metalloproteinases; tissue inhibitors of matrix metalloproteinases