{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:52:22Z","timestamp":1791924742045,"version":"4.3.4"},"reference-count":46,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["mcponline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular & Cellular Proteomics"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.mcpro.2025.101025","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T03:29:58Z","timestamp":1751426998000},"page":"101025","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proteome Profiling of Cerebrospinal Fluid and Machine Learning Reveal Protein Classifiers of Two Forms of Alzheimer\u2019s Disease Characterized by Increased or Not Altered Levels of Tau"],"prefix":"10.1016","volume":"24","author":[{"given":"Elisabetta","family":"Scalia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5330-3537","authenticated-orcid":false,"given":"Matteo","family":"Calligaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Lo Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8262-8223","authenticated-orcid":false,"given":"Salvatore","family":"Castelbuono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"Iemmolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzina","family":"Lo Re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bivona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3410-2067","authenticated-orcid":false,"given":"Tommaso","family":"Piccoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Ghersi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7300-6153","authenticated-orcid":false,"given":"Simone Dario","family":"Scilabra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mcpro.2025.101025_bib1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.mcpro.2025.101025_bib2","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","article-title":"Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk","volume":"51","author":"Jansen","year":"2019","journal-title":"Nat. Genet."},{"key":"10.1016\/j.mcpro.2025.101025_bib3","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/S1474-4422(22)00298-8","article-title":"Advances in Alzheimer's disease research over the past two decades","volume":"21","author":"Jack","year":"2022","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.mcpro.2025.101025_bib4","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s13195-021-00927-z","article-title":"The Alzheimer's disease drug development landscape","volume":"13","author":"van Bokhoven","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.mcpro.2025.101025_bib5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1080\/10408363.2019.1670613","article-title":"Cerebrospinal fluid proteomics and biological heterogeneity in Alzheimer's disease: a literature review","volume":"57","author":"Wesenhagen","year":"2020","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"10.1016\/j.mcpro.2025.101025_bib6","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13024-024-00767-z","article-title":"CSF proteins of inflammation, proteolysis and lipid transport define preclinical AD and progression to AD dementia in cognitively unimpaired individuals","volume":"19","author":"Del Campo","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.mcpro.2025.101025_bib7","doi-asserted-by":"crossref","first-page":"5635","DOI":"10.1038\/s41467-023-41122-y","article-title":"CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer s disease","volume":"14","author":"Del Campo","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mcpro.2025.101025_bib8","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1038\/s43587-022-00300-1","article-title":"CSF proteome profiling across the Alzheimer's disease spectrum reflects the multifactorial nature of the disease and identifies specific biomarker panels","volume":"2","author":"Del Campo","year":"2022","journal-title":"Nat. Aging"},{"key":"10.1016\/j.mcpro.2025.101025_bib9","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1093\/brain\/awad213","article-title":"CSF proteomics in autosomal dominant Alzheimer's disease highlights parallels with sporadic disease","volume":"146","author":"van der Ende","year":"2023","journal-title":"Brain"},{"key":"10.1016\/j.mcpro.2025.101025_bib10","doi-asserted-by":"crossref","first-page":"100577","DOI":"10.1016\/j.mcpro.2023.100577","article-title":"MS-based proteomics of body fluids: the end of the beginning","volume":"22","author":"Bader","year":"2023","journal-title":"Mol. Cell Proteomics"},{"key":"10.1016\/j.mcpro.2025.101025_bib11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.mcpro.2025.101025_bib12","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.neuron.2017.09.025","article-title":"A primer on concepts and applications of proteomics in neuroscience","volume":"96","author":"Hosp","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.mcpro.2025.101025_bib13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s43587-023-00550-7","article-title":"Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles","volume":"4","author":"Tijms","year":"2024","journal-title":"Nat. Aging"},{"key":"10.1016\/j.mcpro.2025.101025_bib14","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1093\/brain\/awaa325","article-title":"Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics","volume":"143","author":"Tijms","year":"2020","journal-title":"Brain"},{"key":"10.1016\/j.mcpro.2025.101025_bib15","doi-asserted-by":"crossref","DOI":"10.1002\/prca.201800105","article-title":"Quantitative proteomic profiling of cerebrospinal fluid to identify candidate biomarkers for alzheimer's disease","volume":"13","author":"Sathe","year":"2019","journal-title":"Proteomics Clin. Appl."},{"key":"10.1016\/j.mcpro.2025.101025_bib16","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aaz9360","article-title":"Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer\u2019s disease","volume":"6","author":"Higginbotham","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.mcpro.2025.101025_bib17","doi-asserted-by":"crossref","DOI":"10.15252\/msb.20199356","article-title":"Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease","volume":"16","author":"Bader","year":"2020","journal-title":"Mol. Syst. Biol."},{"key":"10.1016\/j.mcpro.2025.101025_bib18","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1021\/ac026117i","article-title":"Stop and go extraction tips for matrix-assisted laser desorption\/ionization, nanoelectrospray, and LC\/MS sample pretreatment in proteomics","volume":"75","author":"Rappsilber","year":"2003","journal-title":"Anal. Chem."},{"key":"10.1016\/j.mcpro.2025.101025_bib19","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wisniewski","year":"2009","journal-title":"Nat. Methods"},{"key":"10.1016\/j.mcpro.2025.101025_bib20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13024-022-00521-3","article-title":"Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer\u2019s disease","volume":"17","author":"Visser","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.mcpro.2025.101025_bib21","doi-asserted-by":"crossref","first-page":"5498","DOI":"10.3390\/jcm11195498","article-title":"High cerebrospinal fluid CX3CL1 levels in alzheimer's disease patients but not in non-alzheimer's disease dementia","volume":"11","author":"Bivona","year":"2022","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.mcpro.2025.101025_bib22","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.mcpro.2025.101025_bib23","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimer's Dement."},{"key":"10.1016\/j.mcpro.2025.101025_bib24","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: toward a biological definition of Alzheimer's disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.mcpro.2025.101025_bib25","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"10.1016\/j.mcpro.2025.101025_bib26","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinform."},{"key":"10.1016\/j.mcpro.2025.101025_bib27","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.neuron.2019.05.002","article-title":"SynGO: an evidence-based, expert-curated knowledge base for the synapse","volume":"103","author":"Koopmans","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.mcpro.2025.101025_bib28","first-page":"2825","article-title":"Scikit-learn: machine learning in Python","volume":"12","author":"Fabian","year":"2011","journal-title":"J. Machine Learn. Res."},{"key":"10.1016\/j.mcpro.2025.101025_bib29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.mcpro.2025.101025_bib30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.tips.2021.01.001","article-title":"14-3-3 proteins: novel pharmacological targets in neurodegenerative diseases","volume":"42","author":"Pair","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.mcpro.2025.101025_bib31","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0304-3940(96)12598-2","article-title":"Neurofibrillary tangles of Alzheimer's disease brains contain 14-3-3 proteins","volume":"209","author":"Layfield","year":"1996","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.mcpro.2025.101025_bib32","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3233\/JAD-2011-110692","article-title":"Probable participation of 14-3-3 in tau protein oligomerization and aggregation","volume":"27","author":"Sluchanko","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.mcpro.2025.101025_bib33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s13195-023-01304-8","article-title":"Systematic review: fluid biomarkers and machine learning methods to improve the diagnosis from mild cognitive impairment to Alzheimer's disease","volume":"15","author":"Blanco","year":"2023","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.mcpro.2025.101025_bib34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13024-022-00521-3","article-title":"Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer's disease","volume":"17","author":"Visser","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.mcpro.2025.101025_bib35","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer's disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.mcpro.2025.101025_bib36","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2022.941927","article-title":"Early increase of cerebrospinal fluid 14-3-3zeta protein in the alzheimer's disease continuum","volume":"14","author":"Lu","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.mcpro.2025.101025_bib37","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1007\/s12031-019-01325-9","article-title":"14-3-3\/Tau interaction and tau amyloidogenesis","volume":"68","author":"Chen","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.mcpro.2025.101025_bib38","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13195-022-01113-5","article-title":"Multi-platform proteomic analysis of Alzheimer's disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome","volume":"14","author":"Dammer","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.mcpro.2025.101025_bib39","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s00401-024-02819-6","article-title":"SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Abeta aggregation","volume":"148","author":"Balcomb","year":"2024","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.mcpro.2025.101025_bib40","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s10020-020-00163-5","article-title":"Key role of MIF-related neuroinflammation in neurodegeneration and cognitive impairment in Alzheimer's disease","volume":"26","author":"Nasiri","year":"2020","journal-title":"Mol. Med."},{"key":"10.1016\/j.mcpro.2025.101025_bib41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13195-022-01014-7","article-title":"Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study","volume":"14","author":"Vrillon","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.mcpro.2025.101025_bib42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0896-6273(00)80873-9","article-title":"Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses","volume":"25","author":"Wolpowitz","year":"2000","journal-title":"Neuron"},{"key":"10.1016\/j.mcpro.2025.101025_bib43","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41586-022-05440-3","article-title":"Medin co-aggregates with vascular amyloid-beta in Alzheimer's disease","volume":"612","author":"Wagner","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.mcpro.2025.101025_bib44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0299-y","article-title":"Diagnosis of Alzheimer\u2019s disease utilizing amyloid and tau as fluid biomarkers","volume":"51","author":"Lee","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.mcpro.2025.101025_bib45","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal. Transduction Targeted Ther."},{"key":"10.1016\/j.mcpro.2025.101025_bib46","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early alzheimer's disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N. Engl. J. Med."}],"container-title":["Molecular & Cellular Proteomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1535947625001240?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1535947625001240?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T21:08:47Z","timestamp":1762549727000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1535947625001240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["S1535947625001240"],"URL":"https:\/\/doi.org\/10.1016\/j.mcpro.2025.101025","relation":{},"ISSN":["1535-9476"],"issn-type":[{"value":"1535-9476","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Proteome Profiling of Cerebrospinal Fluid and Machine Learning Reveal Protein Classifiers of Two Forms of Alzheimer\u2019s Disease Characterized by Increased or Not Altered Levels of Tau","name":"articletitle","label":"Article Title"},{"value":"Molecular & Cellular Proteomics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mcpro.2025.101025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology\u00e9","name":"copyright","label":"Copyright"}],"article-number":"101025"}}