{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:03:14Z","timestamp":1790960594751,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["FP7\/2007\u20102013"],"award-info":[{"award-number":["FP7\/2007\u20102013"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Frailty is a clinical state reflecting a decrease in physiological reserve capacities, known to affect numerous biological pathways and is associated with health issues, including neurodegenerative diseases. However, how global protein expression is affected in the central nervous system in frail subject remains underexplored. In this post hoc cross\u2010sectional biomarker analysis, we included 90 adults (52\u201385\u2009years) suspected of normal pressure hydrocephalus (NPH) and presenting with markers of neurodegenerative diseases. We investigated the human proteomic profile of cerebrospinal fluid associated with frailty defined by an established cumulated frailty index (FI, average\u2009=\u20090.32), not enriched for neurology clinical features. Using a label\u2010free quantitative proteomic approach, we identified and quantified 999 proteins of which 13 were positively associated with frailty. Pathway analysis with the top positively frailty\u2010associated proteins revealed enrichment for proteins related to inflammation and immune response. Among the 60 proteins negatively associated with frailty, functional pathways enriched included neurogenesis, synaptogenesis and neuronal guidance. We constructed a frailty prediction model using ridge regression with 932 standardized proteins. Our results showed that the \u201cproteomic model\u201d could become an equivalent predictor of FI in order to study chronological age. This study represents the first comprehensive exploration of the proteomic profile of frailty within cerebrospinal fluid. It sheds light on the physiopathology of frailty, particularly highlighting processes of neuroinflammation and inhibition of neurogenesis. Our findings unveil a range of biological mechanisms that are dysregulated in frailty, in NPH subjects at risk of neurodegenerative impairment, offering new perspectives on frailty phenotyping and prediction.<\/jats:p>","DOI":"10.1111\/acel.14168","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T04:39:29Z","timestamp":1714711169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cerebrospinal fluid proteomic profile of frailty: Results from the <scp>PROLIPHYC<\/scp> cohort"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1721-879X","authenticated-orcid":false,"given":"Sophie","family":"Guillotin","sequence":"first","affiliation":[{"name":"Aging\u2010MAINTAIN Research Team, Center for Epidemiology and Research in POPulation Health (CERPOP) University of Toulouse  Toulouse France"},{"name":"Poison Control Center Toulouse University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Fulzele","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS) University of Toulouse, CNRS, University of Toulouse III (Paul Sabatier (UT3)  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Vallet","sequence":"additional","affiliation":[{"name":"Biological Tissue and Surface Engineering Department INSERM U1059 Sainbiose, Ecole Des Mines of Saint\u2010Etienne  Saint\u2010Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Gonzalez","family":"de Peredo","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS) University of Toulouse, CNRS, University of Toulouse III (Paul Sabatier (UT3)  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Mouton\u2010Barbosa","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS) University of Toulouse, CNRS, University of Toulouse III (Paul Sabatier (UT3)  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Cestac","sequence":"additional","affiliation":[{"name":"Aging\u2010MAINTAIN Research Team, Center for Epidemiology and Research in POPulation Health (CERPOP) University of Toulouse  Toulouse France"},{"name":"Department of Clinical Pharmacy Toulouse University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Andrieu","sequence":"additional","affiliation":[{"name":"Aging\u2010MAINTAIN Research Team, Center for Epidemiology and Research in POPulation Health (CERPOP) University of Toulouse  Toulouse France"},{"name":"Department of Epidemiology and Public Health Toulouse University Hospital  Toulouse France"},{"name":"IHU HealthAge  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Burlet\u2010Schiltz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS) University of Toulouse, CNRS, University of Toulouse III (Paul Sabatier (UT3)  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Delcourt","sequence":"additional","affiliation":[{"name":"Poison Control Center Toulouse University Hospital  Toulouse France"},{"name":"Toulouse NeuroImaging Center (ToNIC) University of Toulouse, INSERM UPS  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Toulouse NeuroImaging Center (ToNIC) University of Toulouse, INSERM UPS  Toulouse France"},{"name":"Department of Neurosurgery Toulouse University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532\u20105415.2012.04142.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20105347(17)36966\u20105"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu117"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2018.07.004"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603\u2010013\u20100396\u2010x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101020"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201307020"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2011.05.014"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/56.3.m146"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.18153"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201002841\u20107"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1113"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1028"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glac074"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010022\u201002572\u20104"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.06.032"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010020\u201000288\u20109"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002093-199509020-00009"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.17627"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13975"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2020.60"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2023.07.147"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201026366\u2010w"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010022\u201004182\u20109"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4861"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.886527"},{"key":"e_1_2_11_30_1","volume-title":"Dementia: Assessment, management and support for people living with dementia and their carers","author":"National Institute for Health and Care Excellence","year":"2018"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/56.7.m448"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13978"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101530"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.neu.0000168185.29659.c5"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2010.08.008"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2013.05.017"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13193"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102318\u20108\u201024"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glr224"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143\u2010019\u201001201\u20105"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.09.223"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.04.009"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12799"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2021"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010019\u201009689\u2010z"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0253976"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2018.05.002"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.10.010"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.696944"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12877\u2010022\u201003454\u20100"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.14168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T08:21:31Z","timestamp":1721377291000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.14168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,2]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/acel.14168"],"URL":"https:\/\/doi.org\/10.1111\/acel.14168","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,2]]},"assertion":[{"value":"2023-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14168"}}