Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer’s Disease

Abstract

This study investigated the diagnostic accuracy of plasma biomarkers—specifically, matrix metalloproteinase (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), CD147, and the MMP-/TIMP-1 ratio in patients with Alzheimer’s disease (AD) dementia. The research cohort comprised patients diagnosed with probable AD dementia and a control group of cognitively unimpaired (CU) individuals. Neuroradiological assessments included brain magnetic resonance imaging (MRI) following dementia protocols, with subsequent volumetric analysis. Additionally, cerebrospinal fluid (CSF) AD biomarkers were classified using the A/T/N system, and apolipoprotein E (APOE) ε4 carrier status was determined. Findings revealed elevated plasma levels of MMP-9 and TIMP-1 in AD dementia patients compared to CU individuals. Receiver operating characteristic (ROC) curve analysis demonstrated significant differences in the areas under the curve (AUC) for MMP-9 (p < 0.001) and TIMP-1 (p < 0.001). Notably, plasma TIMP-1 levels were significantly lower in APOE ε4+ patients than in APOE ε4− patients (p = 0.041). Furthermore, APOE ε4+ patients exhibited reduced hippocampal volume, particularly in total, right, and left hippocampal measurements. TIMP-1 levels exhibited a positive correlation, while the MMP-9/TIMP-1 ratio showed a negative correlation with hippocampal volume parameters. This study sheds light on the potential use of TIMP-1 as a diagnostic marker and its association with hippocampal changes in AD.