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Sixty-one publications reporting metalloproteinase and inhibitor levels in 8576 patients with AD or MCI, and 7333 controls were included in the systematic review, twenty-one of which were extracted for meta-analysis. Standardized mean difference (SMD) was used to illustrate comparisons, and the Newcastle-Ottawa scale to assess bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Higher levels of cerebrospinal fluid (CSF) tissue inhibitor of metalloproteinase-2 (TIMP-2;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0003) were observed in the AD group and in patients with MCI (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0009) compared to cognitively healthy controls. Following sensitivity analysis, significantly higher levels of CSF MMP-10 (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0005) and lower plasma TIMP-2 (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.004) were also noted in patients with AD. TIMP-3, across all sample matrices, was decreased in patients with MCI versus controls (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261456729","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:21:48Z","timestamp":1780730508000},"page":"1127-1142","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["A systematic review and meta-analysis of metalloproteinases in patients with Alzheimer's disease and mild cognitive impairment"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3571-8710","authenticated-orcid":false,"given":"Gillian","family":"McNaugher","sequence":"first","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2927-7570","authenticated-orcid":false,"given":"Leah","family":"McColgan","sequence":"additional","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8377-3766","authenticated-orcid":false,"given":"Mia","family":"Church","sequence":"additional","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-1172","authenticated-orcid":false,"given":"Paula L.","family":"McClean","sequence":"additional","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3547-5551","authenticated-orcid":false,"given":"David S.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0170-6809","authenticated-orcid":false,"given":"Elaine K.","family":"Murray","sequence":"additional","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4726-9530","authenticated-orcid":false,"given":"Sophie","family":"Coyle","sequence":"additional","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-3504","authenticated-orcid":false,"given":"Victoria","family":"McGilligan","sequence":"additional","affiliation":[{"name":"Ulster University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.167"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10737"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.610931"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602440200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.01.003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02790-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2022.147937"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.01.003"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.188"},{"key":"e_1_3_3_11_2","first-page":"908636","article-title":"Matrix metalloproteinases and their multiple roles in Alzheimer's disease","volume":"2014","author":"Wang X","year":"2014","unstructured":"Wang X, Tan M, Yu J, et al. 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