Abstract
Background
Various studies have reported altered expression of metalloproteinases in Alzheimer’s disease (AD); however, expression profiles of each metalloproteinase during cognitive decline have not yet been fully characterised.
Objectives
The purpose of this systematic review was to generate a comprehensive overview of metalloproteinases and their cognate inhibitors expression in AD and Mild Cognitive Impairment (MCI), across sample matrices, to determine whether metalloproteinases are dysregulated in AD and may have predictive power in individuals with cognitive decline.
Methods
An electronic literature search was conducted in PubMed, EMBASE, Scopus and MEDLINE from inception to December 2024. Sixty-one publications reporting metalloproteinase and inhibitor levels in 8,576 patients with AD or MCI, and 7,333 controls were included in the systematic review, twenty-one of which were extracted for meta-analysis. Standardised mean difference (SMD) was used to illustrate comparisons, and the Newcastle-Ottawa scale to assess bias.
Results
Higher levels of cerebrospinal fluid (CSF) tissue inhibitor of metalloproteinase-2 (TIMP-2; p = 0.0003) were observed in the AD group and in patients with MCI (p = 0.0009) compared to cognitively healthy controls. Following sensitivity analysis, significantly higher levels of CSF MMP-10 (p = 0.0005) and lower plasma TIMP-2 (p = 0.004) were also noted in patients with AD. TIMP-3, across all sample matrices, was decreased in patients with MCI versus controls (p = 0.01).
Conclusion
Significantly altered levels of metalloproteinases and their inhibitors were verified between patients with AD and MCI, representing potential biomarkers and prospective therapeutic targets for cognitive decline. This study was registered with PROSPERO, CRD42024628202.
Various studies have reported altered expression of metalloproteinases in Alzheimer’s disease (AD); however, expression profiles of each metalloproteinase during cognitive decline have not yet been fully characterised.
Objectives
The purpose of this systematic review was to generate a comprehensive overview of metalloproteinases and their cognate inhibitors expression in AD and Mild Cognitive Impairment (MCI), across sample matrices, to determine whether metalloproteinases are dysregulated in AD and may have predictive power in individuals with cognitive decline.
Methods
An electronic literature search was conducted in PubMed, EMBASE, Scopus and MEDLINE from inception to December 2024. Sixty-one publications reporting metalloproteinase and inhibitor levels in 8,576 patients with AD or MCI, and 7,333 controls were included in the systematic review, twenty-one of which were extracted for meta-analysis. Standardised mean difference (SMD) was used to illustrate comparisons, and the Newcastle-Ottawa scale to assess bias.
Results
Higher levels of cerebrospinal fluid (CSF) tissue inhibitor of metalloproteinase-2 (TIMP-2; p = 0.0003) were observed in the AD group and in patients with MCI (p = 0.0009) compared to cognitively healthy controls. Following sensitivity analysis, significantly higher levels of CSF MMP-10 (p = 0.0005) and lower plasma TIMP-2 (p = 0.004) were also noted in patients with AD. TIMP-3, across all sample matrices, was decreased in patients with MCI versus controls (p = 0.01).
Conclusion
Significantly altered levels of metalloproteinases and their inhibitors were verified between patients with AD and MCI, representing potential biomarkers and prospective therapeutic targets for cognitive decline. This study was registered with PROSPERO, CRD42024628202.
| Original language | English |
|---|---|
| Pages (from-to) | 1-16 |
| Number of pages | 16 |
| Journal | Journal of Alzheimer's Disease |
| Early online date | 6 Jun 2026 |
| DOIs | |
| Publication status | Published online - 6 Jun 2026 |
Data Availability Statement
No datasets were generated or analyzed during the current studyFunding
This study was funded by a DfE CAST Award in collaboration with Biosynth who sponsored this work.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
-
SDG 3 Good Health and Well-being
Keywords
- Alzheimer’s disease (AD)
- Mild Cognitive Impairment
- tissue inhibitors of matrix metalloproteinases
- Systematic Review
- matrix metalloproteinase
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