Matrix metalloproteinases (
MMPs) and their natural tissue inhibitors (TIMPs) are involved in cell signaling processes and the release of extracellular matrix (ECM) and non-ECM molecules. Nonregulated
MMP activity and an imbalance between
metalloproteinases and their inhibitors might contribute to various disorders, including
neurodegenerative diseases such as
Alzheimer's disease (AD), which is the most common cause of
dementia. There is a complex relationship between
MMPs and TIMPs with AD. It has been shown that
MMPs and TIMPs are localized in neuritic
senile plaques and neurofibrillary tangles in the postmortem brains of patients with AD. Some
MMPs have also been shown to induce tau aggregation and the formation of neurofibrillary tangles in vitro. Moreover,
MMPs contribute to AD pathogenesis via the disruption of the blood-brain barrier and promotion of neurodegeneration. However,
MMPs can degrade both soluble and fibrillar forms of
amyloid-β (Aβ). It has also been shown that Aβ enhances the expression of
MMPs in neuroglial cultures and induces the release of
TIMP-1 by brain cells. Inhibition of Aβ-induced
MMP activity resulted in an improvement of performance tests in mice. Moreover, simultaneous examination of MMP-9, MMP-2, and
TIMP-1 in the CSF contributed to the ability to differentiate between AD and other types of
dementia. Thus, the aim of this literature study was to describe the role of
MMPs and TIMPs in neurodegeneration, as well as their potential usefulness as CSF or plasma
biomarkers in the diagnosis of AD as well as other
neurodegenerative disorders and
vascular dementia.