{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:03:48Z","timestamp":1774940628558,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,10,3]],"date-time":"2021-10-03T00:00:00Z","timestamp":1633219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Beta\u2010secretase 1 (BACE1) is considered as the key enzyme in amyloid\u2010\u03b2 formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late\u2010onset Alzheimer's disease (LOAD) as well as mild cognitive impairment (MCI). Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia. BACE1 activity was measured in the serum of 259\u00a0MCI patients (162 amnestic\u2014aMCI, 97 non\u2010amnestic\u2014naMCI) and 204\u00a0healthy Controls. After a median follow\u2010up of 32\u00a0months (range: 10\u2013153), 116\u00a0MCI progressed to dementia (87 aMCI and 29 naMCI). Serum BACE1 activity was higher in MCI compared with Controls (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001), and in aMCI with brain atrophy compared with naMCI without brain atrophy (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.04). No difference in BACE1 activity emerged between converter and non\u2010converter MCI, and this was true for both aMCI and naMCI. However, among aMCI with better cognitive performance (n. 163, MMSE score \u226524\/30) those converting to dementia had higher BACE1 activity compared to stable ones (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.05). This was not associated with an increased risk to develop dementia (hazard ratio: 1.65; 95% confidence interval: 0.67\u20134.01). In conclusion, serum BACE1 activity significantly increased in MCI patients (both amnestic and non\u2010amnestic) compared with Controls. Moreover, higher serum BACE1 activity was observed only among aMCI with a better cognitive performance who progressed to dementia, suggesting that a dysregulation of this enzyme might be an early event primarily associated with neurodegeneration.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15513-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15513","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T19:15:33Z","timestamp":1631906133000},"page":"629-637","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Serum beta\u2010secretase 1 (BACE1) activity increases in patients with mild cognitive impairment"],"prefix":"10.1111","volume":"159","author":[{"given":"Giovanni","family":"Zuliani","sequence":"first","affiliation":[{"name":"Department of Translational Medicine and for Romagna University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3579-7921","authenticated-orcid":false,"given":"Alessandro","family":"Trentini","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Brombo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and for Romagna University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Rosta","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and for 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Romagna University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Pedrini","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and for Romagna University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Pistolesi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and for Romagna University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Pacifico","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences University of Ferrara Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences University of Ferrara Ferrara 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