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. 2024 May 24;25(11):5703.
doi: 10.3390/ijms25115703.

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

Jelena Bašić  1 , Vuk Milošević  2   3 , Branka Djordjević  1 , Vladana Stojiljković  1 , Milica Živanović  4 , Nikola Stefanović  5 , Aleksandra Aracki Trenkić  2   4 , Dragan Stojanov  2   4 , Tatjana Jevtović Stoimenov  1 , Ivana Stojanović  1
Affiliations

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

Jelena Bašić et al. Int J Mol Sci. .

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.

Keywords: APOE ε4; Alzheimer’s disease; hippocampal volume; matrix metalloproteinase-9; tissue inhibitor of metalloproteinase-1.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Plasma levels of MMP-9 (A), TIMP-1 (B), CD147 (C), and MMP-9/TIMP-1 ratio (D) in the patients and cognitively unimpaired (CU) individuals.
Figure 2
Figure 2
The receiver operating characteristic (ROC) curve analysis for plasma biomarkers.
Figure 3
Figure 3
Plasma levels of TIMP-1 (A), and hippocampal volumes, including total hippocampal volume (B-1), total hippocampal volume/ICV (B-2), right hippocampal volume (C-1), right hippocampal volume/ICV (C-2), and left hippocampal volume (D) in APOE ε4+ and APOE ε4− patients.
Figure 4
Figure 4
Correlation analysis between TIMP-1 and total hippocampal volume (A-1), total hippocampal volume/ICV (A-2), right hippocampal volume (A-3), right hippocampal volume/ICV (A-4), left hippocampal volume (A-5), and left hippocampal volume/ICV (A-6); MMP-9/TIMP-1 ratio and total hippocampal volume (B-1), total hippocampal volume/ICV (B-2), left hippocampal volume (B-3) and left hippocampal volume/ICV (B-4) in AD dementia patients.
See this image and copyright information in PMC

References

    1. Nichols E., Szoeke C.E., Vollset S.E., Abbasi N., Abd-Allah F., Abdela J., Aichour M.T.E., Akinyemi R.O., Alahdab F., Asgedom S.W. Global, Regional, and National Burden of Alzheimer’s Disease and Other Dementias, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:88–106. doi: 10.1016/S1474-4422(18)30403-4. - DOI - PMC - PubMed
    1. Nichols E., Steinmetz J.D., Vollset S.E., Fukutaki K., Chalek J., Abd-Allah F., Abdoli A., Abualhasan A., Abu-Gharbieh E., Akram T.T. Estimation of the Global Prevalence of Dementia in 2019 and Forecasted Prevalence in 2050: An Analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7:e105–e125. doi: 10.1016/S2468-2667(21)00249-8. - DOI - PMC - PubMed
    1. Frisoni G.B., Altomare D., Thal D.R., Ribaldi F., van der Kant R., Ossenkoppele R., Blennow K., Cummings J., van Duijn C., Nilsson P.M. The Probabilistic Model of Alzheimer Disease: The Amyloid Hypothesis Revised. Nat. Rev. Neurosci. 2022;23:53–66. doi: 10.1038/s41583-021-00533-w. - DOI - PMC - PubMed
    1. McKhann G.M., Knopman D.S., Chertkow H., Hyman B.T., Jack Jr C.R., Kawas C.H., Klunk W.E., Koroshetz W.J., Manly J.J., Mayeux R. The Diagnosis of Dementia Due to Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease. Alzheimer’s Dement. 2011;7:263–269. doi: 10.1016/j.jalz.2011.03.005. - DOI - PMC - PubMed
    1. Jack Jr C.R., Bennett D.A., Blennow K., Carrillo M.C., Dunn B., Haeberlein S.B., Holtzman D.M., Jagust W., Jessen F., Karlawish J. NIA-AA Research Framework: Toward a Biological Definition of Alzheimer’s Disease. Alzheimer’s Dement. 2018;14:535–562. doi: 10.1016/j.jalz.2018.02.018. - DOI - PMC - PubMed