{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:13:44Z","timestamp":1784225624767,"version":"3.55.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Finalizzata PE\u20102013\u201002359574\u2010 In vivo asse"],"award-info":[{"award-number":["Ricerca Finalizzata PE\u20102013\u201002359574\u2010 In vivo asse"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Converging translational and clinical research strongly indicates that altered immune and inflammatory homeostasis (neuroinflammation) plays a critical pathophysiological role in Alzheimer's disease (AD), across the clinical <jats:italic>continuum<\/jats:italic>. A dualistic role of neuroinflammation may account for a complex biological phenomenon, representing a potential pharmacological target. Emerging blood\u2010based pathophysiological biomarkers, such as cytokines (Cyt) and interleukins (ILs), have been studied as indicators of neuroinflammation in AD. However, inconsistent results have been reported probably due to a lack of standardization of assays with methodological and analytical differences. We used machine\u2010learning and a cross\u2010validation\u2010based statical workflow to explore and analyze the potential impact of key biological factors, such as age, sex, and apolipoprotein\u2010E (APOE) genotype (the major genetic risk factor for late\u2010onset AD) on Cyt. A set of Cyt was selected based on previous literature, and we investigated any potential association in a pooled cohort of cognitively healthy, mild cognitive impairment (MCI), and AD\u2010like dementia patients. We also performed explorative analyses to extrapolate preliminary clinical insights. We found a robust sex effect on IL12 and an APOE\u2010related difference in IL10, with the latter being also related to the presence of advanced cognitive decline. IL1\u03b2 was the variable most significantly associated with MCI\u2010to\u2010dementia conversion over a 2.5\u00a0year\u2010clinical follow\u2010up. Although preliminary, our data support further clinical research to understand whether plasma Cyt may represent reliable and noninvasive tools serving the investigation of neuroimmune and inflammatory dynamics in AD and to foster biomarker\u2010guided pathway\u2010based therapeutic approaches, within the precision medicine development framework.<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\/jnc15686-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15686","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T08:25:41Z","timestamp":1660206341000},"page":"40-52","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biological determinants of blood\u2010based cytokines in the Alzheimer's disease clinical continuum"],"prefix":"10.1111","volume":"163","author":[{"given":"Alessandro","family":"Galgani","sequence":"first","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vergallo","sequence":"additional","affiliation":[{"name":"Sorbonne University, Alzheimer Precision Medicine (APM), AP\u2010HP Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Campese","sequence":"additional","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Lombardo","sequence":"additional","affiliation":[{"name":"U.O.C. \u201cRisonanza Magnetica Specialistica e Neuroradiologia\u201d Fondazione \u201cG. Monasterio\u201d\u2010 National Research Council\/Tuscany Region  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pavese","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University  Newcastle upon Tyne UK"},{"name":"Institute of clinical Medicine, PET Centre Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Petrozzi","sequence":"additional","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"LoGerfo","sequence":"additional","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Franzini","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Cecchetti","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Puglisi\u2010Allegra","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed  Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla L.","family":"Busceti","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed  Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Tognoni","sequence":"additional","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Baldacci","sequence":"additional","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Lista","sequence":"additional","affiliation":[{"name":"Sorbonne University, Alzheimer Precision Medicine (APM), AP\u2010HP Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital  Paris France"},{"name":"Memory Resources and Research Center (CMRR), Neurology Department Gui de Chauliac University Hospital  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Hampel","sequence":"additional","affiliation":[{"name":"Sorbonne University, Alzheimer Precision Medicine (APM), AP\u2010HP Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fornai","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies University of Pisa  Pisa Italy"},{"name":"IRCCS Neuromed  Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2940-8128","authenticated-orcid":false,"given":"Filippo S.","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Neurology Unit Pisa University Hospital  Pisa Italy"},{"name":"Department of Translational Research and of New Surgical and Medical Technologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00124-X"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","unstructured":"Alzheimer's disease facts and figures. (2021).Alzheimer's & Dementia: The Journal of the Alzheimer's Association 17 327\u2013406.","DOI":"10.1002\/alz.12328"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association(2013)Diagnostic and statistical manual of mental disorders.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30490-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00704-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20266"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00550.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8657-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.11.020"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/brbi.1995.1033"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2013.804622"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.112.1.155"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205017666201130092427"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.12.2308"},{"key":"e_1_2_8_17_1","first-page":"2740","article-title":"Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease","volume":"141","author":"Dani M.","year":"2018","journal-title":"Brain: A Journal of Neurology"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.056"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.07.009"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205014666170317113606"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70090-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.03.003"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-006-0575-6"},{"key":"e_1_2_8_24_1","first-page":"11","volume-title":"Artificial intelligence for Alzheimer's disease: Promise or challenge?","author":"Fabrizio C.","year":"2021"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","unstructured":"FazekasF. ChawlukJ. AlaviA. HurtigH. ZimmermanR.(2012)MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. 10.2214\/ajr.149.2.351 149 351\u2013356.","DOI":"10.2214\/ajr.149.2.351"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0032-9"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-019-01366-5"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02169-0"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","unstructured":"Garc\u00edaV. MollinedaR. A. S\u00e1nchezJ. S.(2009)Index of balanced accuracy: A performance measure for skewed class distributions. Lecture notes in computer science (including subseries lecture notes in artificial intelligence and lecture notes in bioinformatics) 5524 LNCS 441\u2013448.","DOI":"10.1007\/978-3-642-02172-5_57"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00456"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00520-w"},{"key":"e_1_2_8_33_1","first-page":"1","article-title":"The amyloid\u2010\u03b2 pathway in Alzheimer's disease","volume":"2021","author":"Hampel H.","year":"2021","journal-title":"Molecular Psychiatry"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2018.06.001"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3880"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.140.6.566"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01264-w"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2007.88"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3773-11.2011"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.08.008"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316201"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.263"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0920-8"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1932-x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2247-3"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.03.007"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00706.x"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mgene.2016.01.001"},{"key":"e_1_2_8_53_1","article-title":"IL\u20101\u03b2, IL\u20106, TNF\u2010 \u03b1 and CRP in elderly patients with depression or Alzheimer's disease: Systematic Review and Meta\u2010Analysis","volume":"8","author":"Ng A.","year":"2018","journal-title":"Scientific Reports"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-445X.1999.01892.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102790"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1701517114"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01456-w"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.099"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000279336.36610.f7"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20542"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31450"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-319148"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.604000"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0051-1"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00444-1"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-016-0055-4"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-140177"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2020.105708"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.07.001"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.07.009"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.03.009"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15686","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.15686","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15686","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T09:25:34Z","timestamp":1692264334000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.15686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,22]]},"references-count":70,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/jnc.15686"],"URL":"https:\/\/doi.org\/10.1111\/jnc.15686","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,22]]},"assertion":[{"value":"2022-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}