Evaluation of Matrix Metalloproteinase-2 (MMP-2) and -9 (MMP-9) and Their Tissue Inhibitors (TIMP-1 and TIMP-2) in Plasma from Patients with Neurodegenerative Dementia.

Abstract

Matrix metalloproteinases (MMPs) are substantial regulators of learning and memory and might be involved in neurodegeneration. It is known that MMPs are involved in pathogenesis of Alzheimer's disease (AD) and are particularly involved in the amyloid-β processing pathway. However, information on circulating levels of these proteins and their tissue inhibitors (TIMPs) in AD and other neurodegenerative dementia (ND) diseases such as dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) is not clear. Therefore, this study was directed toward finding out how plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 vary in AD, DLB, and FTD; and investigating the correlation of the levels of MMPs and their inhibitors with clinical parameters of the patients. MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were measured by enzyme linked immunosorbent assay (ELISA). Plasma MMP-2 levels were significantly lower in all the patient groups than in the age-matched healthy controls (HCs) (p < 0.05). MMP-9 levels were significantly lower in the FTD patients than in the HCs (p < 0.05). Also, TIMP-1 levels were lower in the AD and FTD patients than in the HCs (p < 0.05). TIMP-2 levels were similar in all the groups. These findings highlight the importance of circulating MMPs in ND and suggest that MMPs and their inhibitors might play a role in impaired amyloid-β peptide metabolism which is responsible for the genesis and progression of ND. Furthermore, measurement of MMP-2 and MMP-9 and their inhibitors may be of great importance for large scale basic research and clinical studies of ND.