Plasma MMP-9/TIMP-1 ratio serves as a novel potential biomarker in Alzheimer’s disease

Abstract

This study aimed to explore the diagnostic potential of plasma MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for Alzheimer's disease (AD). This retrospective study was performed in a cohort consisting of patients with AD (AD group) and cognitive normal subjects (HC group). Cerebrospinal fluid (CSF) classic biomarkers including Aβ42, Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) levels, and plasma MMP-9 and TIMP-1 levels were measured by commercially available ELISA kits, respectively. The differential diagnostic potential of plasma MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio was evaluated using the receiver operating characteristic curve analysis. It was observed that significantly elevated levels of plasma MMP-9 and MMP-9/TIMP-1 ratio in patients with AD than HC. Both MMP-9 and MMP-9/TIMP-1 ratios were negatively correlated with CSF Aβ42/Aβ40 ratio and positively correlated with CSF p-tau in AD group. ROC curve analysis showed better diagnostic accuracy of MMP-9/TIMP-1 ratio than MMP-9 for AD at a cutoff value of 1.35 with an area under the curve of 0.906 and sensitivity and specificity of 95.8% and 75%, respectively. Our findings encourage the use of plasma MMP-9/TIMP-1 ratio as a biomarker in the diagnosis of AD.