{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:27:39Z","timestamp":1789907259110,"version":"4.0.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1007\/s11357-019-00127-6","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T12:03:33Z","timestamp":1574165013000},"page":"159-167","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Serum beta-secretase 1 (BACE1) activity as candidate biomarker for late-onset Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-6300","authenticated-orcid":false,"given":"Carlo","family":"Cervellati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Trentini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Rosta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Passaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juana Maria","family":"Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Bonazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Pacifico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Seripa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Valacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo","family":"Guerini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Zuliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"127_CR1","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.3233\/JAD-170839","volume":"62","author":"N Baazaoui","year":"2018","unstructured":"Baazaoui N, Iqbal K (2018) A novel therapeutic approach to treat Alzheimer\u2019s disease by neurotrophic support during the period of synaptic compensation. J Alzheimers Dis 62:1211\u20131218","journal-title":"J Alzheimers Dis"},{"key":"127_CR2","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1046\/j.0022-3042.2002.00770.x","volume":"80","author":"U Bodendorf","year":"2002","unstructured":"Bodendorf U, Danner S, Fischer F, Stefani M, Sturchler-Pierrat C, Wiederhold KH, Staufenbiel M, Paganetti P (2002) Expression of human beta-secretase in the mouse brain increases the steady-state level of beta-amyloid. J Neurochem 80:799\u2013806","journal-title":"J Neurochem"},{"key":"127_CR3","doi-asserted-by":"publisher","first-page":"D445","DOI":"10.1093\/nar\/gkm881","volume":"36","author":"E Bruford","year":"2008","unstructured":"Bruford E, Lush MJ, Wright MW, Sneddon TP, Povey S, Birney E (2008) The HGNC database in 2008: a resource for the human genome. Nucleic Acids Res 36:D445\u2013D448","journal-title":"Nucleic Acids Res"},{"key":"127_CR4","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.nbd.2005.11.002","volume":"22","author":"DA Butterfield","year":"2006","unstructured":"Butterfield DA, Poon HF, St. Clair D et al (2006) Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer\u2019s disease. Neurobiol Dis 22:223\u2013232","journal-title":"Neurobiol Dis"},{"key":"127_CR5","doi-asserted-by":"publisher","first-page":"365","DOI":"10.2174\/1567205011310040003","volume":"10","author":"C Cervellati","year":"2013","unstructured":"Cervellati C, Cremonini E, Bosi C, Magon S, Zurlo A, Bergamini CM, Zuliani G (2013) Systemic oxidative stress in older patients with mild cognitive impairment or late onset Alzheimer\u2019s disease. Curr Alzheimer Res 10:365\u2013372","journal-title":"Curr Alzheimer Res"},{"key":"127_CR6","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jns.2013.11.041","volume":"337","author":"C Cervellati","year":"2014","unstructured":"Cervellati C, Romani A, Seripa D, Cremonini E, Bosi C, Magon S, Passaro A, Bergamini CM, Pilotto A, Zuliani G (2014a) Oxidative balance, homocysteine, and uric acid levels in older patients with late onset Alzheimer\u2019s disease or vascular dementia. J Neurol Sci 337:156\u2013161","journal-title":"J Neurol Sci"},{"key":"127_CR7","first-page":"309507","volume":"2014","author":"C Cervellati","year":"2014","unstructured":"Cervellati C, Romani A, Seripa D et al (2014b) Systemic oxidative stress and conversion to dementia of elderly patients with mild cognitive impairment. Biomed Res Int 2014:309507","journal-title":"Biomed Res Int"},{"key":"127_CR8","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1515\/cclm-2014-0803","volume":"53","author":"C Cervellati","year":"2015","unstructured":"Cervellati C, Romani A, Bergamini CM, Bosi C, Sanz JM, Passaro A, Zuliani G (2015) PON-1 and ferroxidase activities in older patients with mild cognitive impairment, late onset Alzheimer\u2019s disease or vascular dementia. Clin Chem Lab Med 53:1049\u20131056","journal-title":"Clin Chem Lab Med"},{"key":"127_CR9","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1136\/jim-2015-000017","volume":"64","author":"C Cervellati","year":"2016","unstructured":"Cervellati C, Wood PL, Romani A, Valacchi G, Squerzanti M, Sanz JM, Ortolani B, Zuliani G (2016) Oxidative challenge in Alzheimer\u2019s disease: state of knowledge and future needs. J Investig Med 64:21\u201332","journal-title":"J Investig Med"},{"key":"127_CR10","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/j.1471-4159.2008.05603.x","volume":"107","author":"L Chen","year":"2008","unstructured":"Chen L, Na R, Gu M, Richardson A, Ran Q (2008) Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer\u2019s disease. J Neurochem 107:197\u2013207","journal-title":"J Neurochem"},{"key":"127_CR11","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3233\/JAD-2011-110017","volume":"24","author":"B Decourt","year":"2011","unstructured":"Decourt B, Sabbagh MN (2011) BACE1 as a potential biomarker for Alzheimer\u2019s disease. J Alzheimers Dis 24:53\u201359","journal-title":"J Alzheimers Dis"},{"key":"127_CR12","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1001\/archneur.59.9.1381","volume":"59","author":"H Fukumoto","year":"2002","unstructured":"Fukumoto H, Cheung BS, Hyman BT, Irizarry MC (2002) Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 59:1381\u20131389","journal-title":"Arch Neurol"},{"key":"127_CR13","doi-asserted-by":"publisher","first-page":"4687","DOI":"10.1074\/jbc.M109266200","volume":"277","author":"F Gr\u00fcninger-Leitch","year":"2002","unstructured":"Gr\u00fcninger-Leitch F, Schlatter D, K\u00fcng E, Nelb\u00f6ck P, D\u00f6beli H (2002) Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases. J Biol Chem 277:4687\u20134693","journal-title":"J Biol Chem"},{"key":"127_CR14","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1111\/j.1471-4159.2008.05858.x","volume":"108","author":"M Guglielmotto","year":"2009","unstructured":"Guglielmotto M, Aragno M, Autelli R, Giliberto L, Novo E, Colombatto S, Danni O, Parola M, Smith MA, Perry G, Tamagno E, Tabaton M (2009) The up-regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1\u03b1. J Neurochem 108:1045\u20131056","journal-title":"J Neurochem"},{"key":"127_CR15","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.neurobiolaging.2006.11.003","volume":"29","author":"JA Johnston","year":"2008","unstructured":"Johnston JA, Liu WW, Coulson DTR, Todd S, Murphy S, Brennan S, Foy CJ, Craig D, Irvine GB, Passmore AP (2008) Platelet \u03b2-secretase activity is increased in Alzheimer\u2019s disease. Neurobiol Aging 29:661\u2013668","journal-title":"Neurobiol Aging"},{"key":"127_CR16","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/j.1471-4159.2008.05753.x","volume":"108","author":"WW Liu","year":"2009","unstructured":"Liu WW, Todd S, Coulson DTR, Irvine GB, Passmore AP, McGuinness B, McConville M, Craig D, Johnston JA (2009) A novel reciprocal and biphasic relationship between membrane cholesterol and beta-secretase activity in SH-SY5Y cells and in human platelets. J Neurochem 108:341\u2013349","journal-title":"J Neurochem"},{"key":"127_CR17","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/85059","volume":"4","author":"Y Luo","year":"2001","unstructured":"Luo Y, Bolon B, Kahn S, Bennett BD, Babu-Khan S, Denis P, Fan W, Kha H, Zhang J, Gong Y, Martin L, Louis JC, Yan Q, Richards WG, Citron M, Vassar R (2001) Mice deficient in BACE1, the Alzheimer\u2019s beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat Neurosci 4:231\u2013232","journal-title":"Nat Neurosci"},{"key":"127_CR18","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging\u2013Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement 7:263\u2013269","journal-title":"Alzheimers Dement"},{"key":"127_CR19","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.bbadis.2014.04.012","volume":"1842","author":"JK Morris","year":"2014","unstructured":"Morris JK, Honea RA, Vidoni ED, Swerdlow RH, Burns JM (2014) Is Alzheimer\u2019s disease a systemic disease? Biochim Biophys Acta 1842:1340\u20131349","journal-title":"Biochim Biophys Acta"},{"key":"127_CR20","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.bbadis.2012.01.009","volume":"1822","author":"F Mouton-Liger","year":"2012","unstructured":"Mouton-Liger F, Paquet C, Dumurgier J, Bouras C, Pradier L, Gray F, Hugon J (2012) Oxidative stress increases BACE1 protein levels through activation of the PKR-eIF2\u03b1 pathway. Biochim Biophys Acta 1822:885\u2013896","journal-title":"Biochim Biophys Acta"},{"key":"127_CR21","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1159\/000489847","volume":"8","author":"CG Schipke","year":"2018","unstructured":"Schipke CG, De Vos A, Fuentes M et al (2018) Neurogranin and BACE1 in CSF as potential biomarkers differentiating depression with cognitive deficits from early Alzheimer\u2019s disease: a pilot study. Dement Geriatr Cogn Dis Extra 8:277\u2013289","journal-title":"Dement Geriatr Cogn Dis Extra"},{"key":"127_CR22","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.nbd.2013.07.005","volume":"59","author":"M Schrag","year":"2013","unstructured":"Schrag M, Mueller C, Zabel M, Crofton A, Kirsch WM, Ghribi O, Squitti R, Perry G (2013) Oxidative stress in blood in Alzheimer\u2019s disease and mild cognitive impairment: a meta-analysis. Neurobiol Dis 59:100\u2013110","journal-title":"Neurobiol Dis"},{"key":"127_CR23","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.biopsych.2017.02.007","volume":"83","author":"Y Shen","year":"2018","unstructured":"Shen Y, Wang H, Sun Q, Yao H, Keegan AP, Mullan M, Wilson J, Lista S, Leyhe T, Laske C, Rujescu D, Levey A, Wallin A, Blennow K, Li R, Hampel H (2018) Increased plasma beta-secretase 1 may predict conversion to Alzheimer\u2019s disease dementia in individuals with mild cognitive impairment. Biol Psychiatry 83:447\u2013455","journal-title":"Biol Psychiatry"},{"key":"127_CR24","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1523\/JNEUROSCI.17-08-02653.1997","volume":"17","author":"MA Smith","year":"1997","unstructured":"Smith MA, Richey Harris PL, Sayre LM, Beckman JS, Perry G (1997) Widespread peroxynitrite-mediated damage in Alzheimer\u2019s disease. J Neurosci 17:2653\u20132657","journal-title":"J Neurosci"},{"key":"127_CR25","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s10863-009-9241-7","volume":"41","author":"R Sultana","year":"2009","unstructured":"Sultana R, Butterfield DA (2009) Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment. J Bioenerg Biomembr 41:441\u2013446","journal-title":"J Bioenerg Biomembr"},{"key":"127_CR26","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/s12640-011-9283-6","volume":"22","author":"E Tamagno","year":"2012","unstructured":"Tamagno E, Guglielmotto M, Monteleone D, Tabaton M (2012) Amyloid-\u03b2 production: major link between oxidative stress and BACE1. Neurotox Res 22:208\u2013219","journal-title":"Neurotox Res"},{"key":"127_CR27","doi-asserted-by":"publisher","first-page":"e61246","DOI":"10.1371\/journal.pone.0061246","volume":"8","author":"J-L Tan","year":"2013","unstructured":"Tan J-L, Li Q-X, Ciccotosto GD et al (2013) Mild oxidative stress induces redistribution of BACE1 in non-apoptotic conditions and promotes the amyloidogenic processing of Alzheimer\u2019s disease amyloid precursor protein. PLoS One 8:e61246","journal-title":"PLoS One"},{"key":"127_CR28","doi-asserted-by":"publisher","first-page":"65","DOI":"10.2217\/bmm.09.84","volume":"4","author":"M Thambisetty","year":"2010","unstructured":"Thambisetty M, Lovestone S (2010) Blood-based biomarkers of Alzheimer\u2019s disease: challenging but feasible. Biomark Med 4:65\u201379","journal-title":"Biomark Med"},{"key":"127_CR29","doi-asserted-by":"publisher","first-page":"858","DOI":"10.3389\/fphys.2018.00858","volume":"9","author":"G Valacchi","year":"2018","unstructured":"Valacchi G, Virgili F, Cervellati C, Pecorelli A (2018) OxInflammation: from subclinical condition to pathological biomarker. Front Physiol 9:858","journal-title":"Front Physiol"},{"key":"127_CR30","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1126\/science.286.5440.735","volume":"286","author":"R Vassar","year":"1999","unstructured":"Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M (1999) Beta-secretase cleavage of Alzheimer\u2019s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286:735\u2013741","journal-title":"Science"},{"key":"127_CR31","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.jneumeth.2018.10.025","volume":"319","author":"H Zetterberg","year":"2019","unstructured":"Zetterberg H (2019) Blood-based biomarkers for Alzheimer\u2019s disease\u2014an update. J Neurosci Methods 319:2\u20136","journal-title":"J Neurosci Methods"},{"key":"127_CR32","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1001\/archneur.65.8.1102","volume":"65","author":"H Zetterberg","year":"2008","unstructured":"Zetterberg H, Andreasson U, Hansson O, Wu G, Sankaranarayanan S, Andersson ME, Buchhave P, Londos E, Umek RM, Minthon L, Simon AJ, Blennow K (2008) Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol 65:1102\u20131107","journal-title":"Arch Neurol"},{"key":"127_CR33","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1001\/archpsyc.64.6.718","volume":"64","author":"Z Zhong","year":"2007","unstructured":"Zhong Z, Ewers M, Teipel S, B\u00fcrger K, Wallin A, Blennow K, He P, McAllister C, Hampel H, Shen Y (2007) Levels of beta-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. Arch Gen Psychiatry 64:718\u2013726","journal-title":"Arch Gen Psychiatry"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-019-00127-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11357-019-00127-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-019-00127-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T04:39:16Z","timestamp":1605674356000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11357-019-00127-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,19]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["127"],"URL":"https:\/\/doi.org\/10.1007\/s11357-019-00127-6","relation":{},"ISSN":["2509-2715","2509-2723"],"issn-type":[{"value":"2509-2715","type":"print"},{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,19]]},"assertion":[{"value":"24 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}