{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:48Z","timestamp":1792785828363,"version":"4.5.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":61,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG17644"],"award-info":[{"award-number":["R01AG17644"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["198\/1074-02"],"award-info":[{"award-number":["198\/1074-02"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Aging"},{"DOI":"10.13039\/501100023864","name":"NIA","doi-asserted-by":"publisher","award":["R01AG17644"],"award-info":[{"award-number":["R01AG17644"]}],"id":[{"id":"10.13039\/501100023864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023864","name":"NIA","doi-asserted-by":"publisher","award":["R01AG17644"],"award-info":[{"award-number":["R01AG17644"]}],"id":[{"id":"10.13039\/501100023864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00019\/3"],"award-info":[{"award-number":["MC_UU_00019\/3"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Population-based proteomics offers a groundbreaking avenue to predict future disease risks, enhance our understanding of disease mechanisms, and discover novel therapeutic targets and biomarkers. The role of plasma proteins in dementia, however, requires further exploration. This study investigated 276 protein-dementia associations in 229 incident all-cause dementia, 89 Alzheimer\u2019s disease, and 41 vascular dementia among 3249 participants (55% women, 97.2% white ethnicity) from the English Longitudinal Study of Ageing (ELSA) over a median 9.8-year follow-up. We used Cox proportional hazard regression for the analysis. Receiver operating characteristic analyses were conducted to assess the precision of the identified proteins from the fully adjusted Cox regression models in predicting incident all-cause dementia, both individually and in combination with demographic predictors, APOE genotype, and memory score, to estimate the area under the curve. Additionally, the eXtreme Gradient Boosting machine learning algorithm was used to identify the most important features predictive of future all-cause dementia onset. These associations were then validated in 1506 incident all-cause dementia, 732 Alzheimer\u2019s disease, 281 vascular dementia, and 111 frontotemporal dementia cases among 52 745 individuals (53.9% women, 93.3% White ethnicity) from the UK Biobank over a median 13.7-year follow-up. Two-sample bi-directional Mendelian randomization and drug target Mendelian randomization were further employed to determine the causal direction between protein concentration and dementia. NEFL (hazard ratio [HR] [95% confidence intervals (CIs)]: 1.54 [1.29, 1.84]) and RPS6KB1 (HR [95% CI]: 1.33 [1.16, 1.52]) were robustly associated with incident all-cause dementia; MMP12 (HR [95% CI]: 2.06 [1.41, 2.99]) was associated with vascular dementia in ELSA, after correcting for multiple testing. Additional markers EDA2R and KIM1 were identified from subgroup and sensitivity analyses. Combining NEFL and RPS6KB1 with other predictors yielded high predictive accuracy (area under the curve = 0.871) for incident all-cause dementia. The eXtreme Gradient Boosting machine learning algorithm also identified RPS6KB1, NEFL, and KIM1 as the most important protein features for predicting future all-cause dementia. Sex difference was evident for the association between RPS6KB1 and all-cause dementia, with stronger association in men (P for interaction = 0.037). Replication in the UK Biobank confirmed the associations between the identified proteins and various dementia subtypes. The results from Mendelian randomization in the reverse direction indicated that several proteins serve as early markers for dementia, rather than being direct causes of the disease. These findings provide insights into putative mechanisms for dementia. Future studies are needed to validate the findings on RPS6KB1 in relation to dementia risk.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf097","type":"journal-article","created":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T15:12:45Z","timestamp":1740928365000},"source":"Crossref","is-referenced-by-count":11,"title":["Unraveling the role of proteins in dementia: insights from two UK cohorts with causal evidence"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-7640","authenticated-orcid":false,"given":"Jessica","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London , London WC1E 7HB ,","place":["UK"]},{"name":"George Institute for Global Health, Imperial College London , London W12 7RZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan M","family":"Williams","sequence":"additional","affiliation":[{"name":"MRC Unit for Lifelong Health & Ageing, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Scholes","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Assaad","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2060-3768","authenticated-orcid":false,"given":"Feifei","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Behavioural Science and Health, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabina","family":"Hayat","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3036-0499","authenticated-orcid":false,"given":"Paola","family":"Zaninotto","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-4943","authenticated-orcid":false,"given":"Andrew","family":"Steptoe","sequence":"additional","affiliation":[{"name":"Department of Behavioural Science and Health, University College London , London WC1E 7HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"issue":"12","key":"2025032523070085100_fcaf097-B1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41577-018-0051-1","article-title":"Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight","volume":"18","author":"Shi","year":"2018","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"2025032523070085100_fcaf097-B2","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41591-019-0440-4","article-title":"Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1","volume":"25","author":"Yousef","year":"2019","journal-title":"Nat Med"},{"issue":"1","key":"2025032523070085100_fcaf097-B3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41576-020-0268-2","article-title":"Genetics meets proteomics: Perspectives for large population-based studies","volume":"22","author":"Suhre","year":"2021","journal-title":"Nat Rev Genet"},{"issue":"4","key":"2025032523070085100_fcaf097-B4","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/alz.12419","article-title":"Plasma proteins, cognitive decline, and 20-year risk of dementia in the whitehall II and atherosclerosis risk in communities studies","volume":"18","author":"Lindbohm","year":"2022","journal-title":"Alzheimers Dement"},{"issue":"26","key":"2025032523070085100_fcaf097-B5","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1056\/NEJMra2204787","article-title":"Artificial intelligence in molecular medicine","volume":"388","author":"Gomes","year":"2023","journal-title":"N Engl J Med"},{"issue":"1","key":"2025032523070085100_fcaf097-B6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S1474-4422(21)00361-6","article-title":"Blood-based biomarkers for Alzheimer's disease: Towards clinical implementation","volume":"21","author":"Teunissen","year":"2022","journal-title":"Lancet Neurol"},{"issue":"9","key":"2025032523070085100_fcaf097-B7","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/alz.12618","article-title":"Biofluid-based biomarkers for Alzheimer's disease\u2013related pathologies: An update and synthesis of the literature","volume":"18","author":"Zetterberg","year":"2022","journal-title":"Alzheimers Dement"},{"issue":"6569","key":"2025032523070085100_fcaf097-B8","doi-asserted-by":"crossref","first-page":"eabj1541","DOI":"10.1126\/science.abj1541","article-title":"Mapping the proteo-genomic convergence of human diseases","volume":"374","author":"Pietzner","year":"2021","journal-title":"Science"},{"issue":"5","key":"2025032523070085100_fcaf097-B9","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s43587-021-00064-0","article-title":"Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk","volume":"1","author":"Walker","year":"2021","journal-title":"Nat Aging"},{"issue":"705","key":"2025032523070085100_fcaf097-B10","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adf5681","article-title":"Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life","volume":"15","author":"Walker","year":"2023","journal-title":"Sci Transl Med"},{"issue":"1","key":"2025032523070085100_fcaf097-B11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrd.2016.230","article-title":"A comprehensive map of molecular drug targets","volume":"16","author":"Santos","year":"2017","journal-title":"Nat Rev Drug Discov"},{"issue":"7","key":"2025032523070085100_fcaf097-B12","doi-asserted-by":"crossref","first-page":"100786","DOI":"10.1016\/j.mcpro.2024.100786","article-title":"Promises and challenges of populational proteomics in health and disease","volume":"23","author":"Sun","year":"2024","journal-title":"Mol Cell Proteomics"},{"issue":"4","key":"2025032523070085100_fcaf097-B13","doi-asserted-by":"crossref","first-page":"e95192","DOI":"10.1371\/journal.pone.0095192","article-title":"Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability","volume":"9","author":"Assarsson","year":"2014","journal-title":"PLoS One"},{"issue":"1-1","key":"2025032523070085100_fcaf097-B14","article-title":"Aptamer-based multiplexed proteomic technology for biomarker discovery","author":"Gold","year":"2010","journal-title":"Nat Preced"},{"key":"2025032523070085100_fcaf097-B15","doi-asserted-by":"crossref","first-page":"n1804","DOI":"10.1136\/bmj.n1804","article-title":"Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: Three analyses of population cohort studies","volume":"374","author":"Kivim\u00e4ki","year":"2021","journal-title":"BMJ"},{"issue":"2","key":"2025032523070085100_fcaf097-B16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s43587-023-00565-0","article-title":"Plasma proteomic profiles predict future dementia in healthy adults","volume":"4","author":"Guo","year":"2024","journal-title":"Nat Aging"},{"issue":"7","key":"2025032523070085100_fcaf097-B17","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s43587-024-00655-7","article-title":"Blood protein assessment of leading incident diseases and mortality in the UK biobank","volume":"4","author":"Gadd","year":"2024","journal-title":"Nat Aging"},{"issue":"1","key":"2025032523070085100_fcaf097-B18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/alz.12369","article-title":"Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer's disease screening and staging","volume":"18","author":"Jiang","year":"2022","journal-title":"Alzheimers Dement"},{"issue":"7982","key":"2025032523070085100_fcaf097-B19","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41586-023-06563-x","article-title":"Large-scale plasma proteomics comparisons through genetics and disease associations","volume":"622","author":"Eldjarn","year":"2023","journal-title":"Nature"},{"issue":"7982","key":"2025032523070085100_fcaf097-B20","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature"},{"issue":"6","key":"2025032523070085100_fcaf097-B21","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1093\/ije\/dys168","article-title":"Cohort profile: The English longitudinal study of ageing","volume":"42","author":"Steptoe","year":"2013","journal-title":"Int J Epidemiol"},{"key":"2025032523070085100_fcaf097-B22","doi-asserted-by":"crossref","first-page":"100168","DOI":"10.1016\/j.mcpro.2021.100168","article-title":"Proximity extension assay in combination with next-generation sequencing for high-throughput proteome-wide analysis","volume":"20","author":"Wik","year":"2021","journal-title":"Mol Cell Proteomics"},{"issue":"7","key":"2025032523070085100_fcaf097-B23","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1111\/jgs.16406","article-title":"Interplay between socioeconomic markers and polygenic predisposition on timing of dementia diagnosis","volume":"68","author":"Ajnakina","year":"2020","journal-title":"J Am Geriatr Soc"},{"issue":"4","key":"2025032523070085100_fcaf097-B24","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1212\/WNL.41.4.479","article-title":"The consortium to establish a registry for Alzheimer's disease (CERAD) part II. Standardization of the neuropathologic assessment of Alzheimer's disease","volume":"41","author":"Mirra","year":"1991","journal-title":"Neurology"},{"key":"2025032523070085100_fcaf097-B25","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s10654-019-00499-1","article-title":"Identifying dementia outcomes in UK biobank: A validation study of primary care, hospital admissions and mortality data","volume":"34","author":"Wilkinson","year":"2019","journal-title":"Eur J Epidemiol"},{"key":"2025032523070085100_fcaf097-B26","volume-title":"Chu G. Impute: Impute: Imputation for microarray data","author":"Hastie","year":"2020"},{"key":"2025032523070085100_fcaf097-B27","first-page":"1","article-title":"Mice: Multivariate imputation by chained equations in R","volume":"45","author":"Van Buuren","year":"2011","journal-title":"J Stat Softw"},{"issue":"19","key":"2025032523070085100_fcaf097-B28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.17485\/ijst\/2017\/v10i19\/110646","article-title":"A comparison of multiple imputation methods for data with missing values","volume":"10","author":"Chhabra","year":"2017","journal-title":"Indian J Sci Technol"},{"issue":"446","key":"2025032523070085100_fcaf097-B29","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","article-title":"A proportional hazards model for the subdistribution of a competing risk","volume":"94","author":"Fine","year":"1999","journal-title":"J Am Stat Assoc"},{"issue":"24","key":"2025032523070085100_fcaf097-B30","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1001\/jama.2024.4970","article-title":"Accounting for competing risks in clinical research","volume":"331","author":"Austin","year":"2024","journal-title":"JAMA"},{"key":"2025032523070085100_fcaf097-B31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J Stat Softw"},{"key":"2025032523070085100_fcaf097-B32","volume-title":"Package \u2018boot\u2019","author":"Canty","year":"2017"},{"key":"2025032523070085100_fcaf097-B33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: An open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"11","key":"2025032523070085100_fcaf097-B34","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1038\/s41562-024-01963-z","article-title":"The genetic landscape of neuro-related proteins in human plasma","volume":"8","author":"Repetto","year":"2024","journal-title":"Nat Hum Behav"},{"issue":"1","key":"2025032523070085100_fcaf097-B35","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/ana.25642","article-title":"Lipid lowering and Alzheimer disease risk: A Mendelian randomization study","volume":"87","author":"Williams","year":"2020","journal-title":"Ann Neurol"},{"issue":"5","key":"2025032523070085100_fcaf097-B36","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1093\/ije\/dyw088","article-title":"Selecting instruments for Mendelian randomization in the wake of genome-wide association studies","volume":"45","author":"Swerdlow","year":"2016","journal-title":"Int J Epidemiol"},{"issue":"2","key":"2025032523070085100_fcaf097-B37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ajhg.2022.12.017","article-title":"Using genetic association data to guide drug discovery and development: Review of methods and applications","volume":"110","author":"Burgess","year":"2023","journal-title":"Am J Hum Genet"},{"issue":"4","key":"2025032523070085100_fcaf097-B38","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1111\/biom.13888","article-title":"Conditional inference in cis-Mendelian randomization using weak genetic factors","volume":"79","author":"Patel","year":"2023","journal-title":"Biometrics"},{"key":"2025032523070085100_fcaf097-B39","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 Bioinformatics"},{"issue":"1","key":"2025032523070085100_fcaf097-B40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"issue":"suppl_1","key":"2025032523070085100_fcaf097-B41","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkm882","article-title":"KEGG for linking genomes to life and the environment","volume":"36","author":"Kanehisa","year":"2007","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"2025032523070085100_fcaf097-B42","first-page":"D498","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2025032523070085100_fcaf097-B43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nrd.2017.252","article-title":"Glimmers in illuminating the druggable genome","volume":"17","author":"Rodgers","year":"2018","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"2025032523070085100_fcaf097-B44","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41587-022-01539-0","article-title":"A proteome-wide atlas of drug mechanism of action","volume":"41","author":"Mitchell","year":"2023","journal-title":"Nat Biotechnol"},{"issue":"6509","key":"2025032523070085100_fcaf097-B45","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Consortium","year":"2020","journal-title":"Science"},{"issue":"D1","key":"2025032523070085100_fcaf097-B46","doi-asserted-by":"crossref","first-page":"D1302","DOI":"10.1093\/nar\/gkaa1027","article-title":"Open targets platform: Supporting systematic drug\u2013target identification and prioritisation","volume":"49","author":"Ochoa","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"2025032523070085100_fcaf097-B47","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1136\/jclinpath-2014-202560","article-title":"P70 ribosomal protein S6 kinase (Rps6kb1): An update","volume":"67","author":"Bahrami-B","year":"2014","journal-title":"J Clin Pathol"},{"issue":"6","key":"2025032523070085100_fcaf097-B48","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/s43587-023-00416-y","article-title":"Targeting the biology of aging with mTOR inhibitors","volume":"3","author":"Mannick","year":"2023","journal-title":"Nat Aging"},{"issue":"9","key":"2025032523070085100_fcaf097-B49","doi-asserted-by":"crossref","first-page":"e12845","DOI":"10.1371\/journal.pone.0012845","article-title":"Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease","volume":"5","author":"Ma","year":"2010","journal-title":"PLoS One"},{"issue":"49","key":"2025032523070085100_fcaf097-B50","doi-asserted-by":"crossref","first-page":"11300","DOI":"10.1523\/JNEUROSCI.2270-05.2005","article-title":"Control of dendritic arborization by the phosphoinositide-3\u2032-kinase\u2013akt\u2013mammalian target of rapamycin pathway","volume":"25","author":"Jaworski","year":"2005","journal-title":"J Neurosci"},{"issue":"2","key":"2025032523070085100_fcaf097-B51","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.tins.2009.11.003","article-title":"mTOR signaling: At the crossroads of plasticity, memory and disease","volume":"33","author":"Hoeffer","year":"2010","journal-title":"Trends Neurosci"},{"key":"2025032523070085100_fcaf097-B52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/2051-5960-1-3","article-title":"Dysfunction of the mTOR pathway is a risk factor for Alzheimer\u2019s disease","volume":"1","author":"Yates","year":"2013","journal-title":"Acta Neuropathol Commun"},{"key":"2025032523070085100_fcaf097-B53","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-981-15-0602-4_3","article-title":"Regulation of autophagy by mTOR signaling pathway","volume":"1206","author":"Wang","year":"2019","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"2025032523070085100_fcaf097-B54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20110892","article-title":"Regulation and function of ribosomal protein S6 kinase (S6 K) within mTOR signalling networks","volume":"441","author":"Magnuson","year":"2012","journal-title":"Biochem J"},{"issue":"2","key":"2025032523070085100_fcaf097-B55","doi-asserted-by":"crossref","first-page":"NS20180203","DOI":"10.1042\/NS20180203","article-title":"The role of APOE4 in Alzheimer\u2019s disease: Strategies for future therapeutic interventions","volume":"3","author":"Hunsberger","year":"2019","journal-title":"Neuronal Signal"},{"issue":"7","key":"2025032523070085100_fcaf097-B56","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.febslet.2010.01.017","article-title":"mTOR regulation of autophagy","volume":"584","author":"Jung","year":"2010","journal-title":"FEBS Lett"},{"key":"2025032523070085100_fcaf097-B57","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12920-020-0689-y","article-title":"Differential co-expression analysis reveals early stage transcriptomic decoupling in Alzheimer\u2019s disease","volume":"13","author":"Upadhyaya","year":"2020","journal-title":"BMC Med Genomics"},{"issue":"30","key":"2025032523070085100_fcaf097-B58","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.1523\/JNEUROSCI.0931-17.2017","article-title":"The mTOR substrate S6 kinase 1 (S6K1) is a negative regulator of axon regeneration and a potential drug target for central nervous system injury","volume":"37","author":"Al-Ali","year":"2017","journal-title":"J Neurosci"},{"issue":"1","key":"2025032523070085100_fcaf097-B59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00021.2015","article-title":"Mechanistic pathways of sex differences in cardiovascular disease","volume":"97","author":"Regitz-Zagrosek","year":"2017","journal-title":"Physiol Rev"},{"key":"2025032523070085100_fcaf097-B60","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s12672-018-0329-6","article-title":"Adiposity results in metabolic and inflammation differences in premenopausal and postmenopausal women consistent with the difference in breast cancer risk","volume":"9","author":"Zhao","year":"2018","journal-title":"Horm Cancer"},{"issue":"5","key":"2025032523070085100_fcaf097-B61","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1089\/neu.2016.4496","article-title":"Serum neurofilament light protein as a marker for diffuse axonal injury: Results from a case series study","volume":"34","author":"Ljungqvist","year":"2017","journal-title":"J Neurotrauma"},{"issue":"613","key":"2025032523070085100_fcaf097-B62","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abg9922","article-title":"Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury","volume":"13","author":"Graham","year":"2021","journal-title":"Sci Transl Med"},{"issue":"3","key":"2025032523070085100_fcaf097-B63","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1001\/jamaneurol.2018.3746","article-title":"Association of cerebrospinal fluid neurofilament light protein levels with cognition in patients with dementia, motor neuron disease, and movement disorders","volume":"76","author":"Olsson","year":"2019","journal-title":"JAMA Neurol"},{"issue":"1","key":"2025032523070085100_fcaf097-B64","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.1038\/s41467-021-23620-z","article-title":"A multicentre validation study of the diagnostic value of plasma neurofilament light","volume":"12","author":"Ashton","year":"2021","journal-title":"Nat Commun"},{"key":"2025032523070085100_fcaf097-B65","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13195-021-00944-y","article-title":"Comparison of plasma neurofilament light and total tau as neurodegeneration markers: Associations with cognitive and neuroimaging outcomes","volume":"13","author":"Marks","year":"2021","journal-title":"Alzheimers Res Ther"},{"issue":"5","key":"2025032523070085100_fcaf097-B66","doi-asserted-by":"crossref","first-page":"e671","DOI":"10.1212\/WNL.0000000000011226","article-title":"Plasma tau and neurofilament light in frontotemporal lobar degeneration and Alzheimer disease","volume":"96","author":"Ill\u00e1n-Gala","year":"2021","journal-title":"Neurology"},{"issue":"22","key":"2025032523070085100_fcaf097-B67","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1212\/WNL.0000000000004683","article-title":"Monitoring disease activity in multiple sclerosis using serum neurofilament light protein","volume":"89","author":"Novakova","year":"2017","journal-title":"Neurology"},{"key":"2025032523070085100_fcaf097-B68","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ebiom.2015.11.036","article-title":"Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: A cross-sectional study","volume":"3","author":"Gissl\u00e9n","year":"2016","journal-title":"EBioMedicine"},{"issue":"9","key":"2025032523070085100_fcaf097-B69","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1001\/archneur.63.9.1277","article-title":"Neurochemical aftermath of amateur boxing","volume":"63","author":"Zetterberg","year":"2006","journal-title":"Arch Neurol"},{"issue":"3","key":"2025032523070085100_fcaf097-B70","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/jnnp-2013-307454","article-title":"Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome","volume":"86","author":"Kuhle","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"6","key":"2025032523070085100_fcaf097-B71","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41593-020-0635-5","article-title":"Shared proteomic effects of cerebral atherosclerosis and Alzheimer\u2019s disease on the human brain","volume":"23","author":"Wingo","year":"2020","journal-title":"Nat Neurosci"},{"issue":"1","key":"2025032523070085100_fcaf097-B72","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.cellbio.17.1.463","article-title":"How matrix metalloproteinases regulate cell behavior","volume":"17","author":"Sternlicht","year":"2001","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2025032523070085100_fcaf097-B73","doi-asserted-by":"crossref","first-page":"928315","DOI":"10.1155\/2013\/928315","article-title":"Matrix metalloproteinases: Inflammatory regulators of cell behaviors in vascular formation and remodeling","volume":"2013","author":"Chen","year":"2013","journal-title":"Mediators Inflamm"},{"key":"2025032523070085100_fcaf097-B74","doi-asserted-by":"crossref","first-page":"620581","DOI":"10.1155\/2015\/620581","article-title":"Friends or foes: Matrix metalloproteinases and their multifaceted roles in neurodegenerative diseases","volume":"2015","author":"Brkic","year":"2015","journal-title":"Mediators Inflamm"},{"key":"2025032523070085100_fcaf097-B75","doi-asserted-by":"crossref","first-page":"42109","DOI":"10.3389\/fneur.2013.00032","article-title":"Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke","volume":"4","author":"Lakhan","year":"2013","journal-title":"Front Neurol"},{"issue":"4","key":"2025032523070085100_fcaf097-B76","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3233\/JAD-2011-101974","article-title":"Investigation of matrix metalloproteinases, MMP-2 and MMP-9, in plasma reveals a decrease of MMP-2 in Alzheimer's disease","volume":"26","author":"Lim","year":"2011","journal-title":"J Alzheimers Dis"},{"issue":"3","key":"2025032523070085100_fcaf097-B77","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0197-0186(03)00004-4","article-title":"Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer\u2019s disease","volume":"43","author":"Lorenzl","year":"2003","journal-title":"Neurochem Int"},{"issue":"4","key":"2025032523070085100_fcaf097-B78","first-page":"6248","article-title":"MMP-3 And MMP-9 concentrations in Alzheimer\u2019s disease: A cerebrospinal fluid and Serum analysis","volume":"30","author":"Perveen","year":"2024","journal-title":"Educ Adm Theory Pract"},{"issue":"5","key":"2025032523070085100_fcaf097-B79","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1161\/01.STR.32.5.1162","article-title":"White matter damage is associated with matrix metalloproteinases in vascular dementia","volume":"32","author":"Rosenberg","year":"2001","journal-title":"Stroke"},{"issue":"2","key":"2025032523070085100_fcaf097-B80","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1161\/STROKEAHA.111.627562","article-title":"Amyloid-\u03b2 contributes to blood\u2013brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy","volume":"43","author":"Hartz","year":"2012","journal-title":"Stroke"},{"issue":"27","key":"2025032523070085100_fcaf097-B81","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1056\/NEJMoa0904006","article-title":"MMP12, lung function, and COPD in high-risk populations","volume":"361","author":"Hunninghake","year":"2009","journal-title":"N Engl J Med"},{"issue":"11","key":"2025032523070085100_fcaf097-B82","doi-asserted-by":"crossref","first-page":"3946","DOI":"10.3390\/ijms21113946","article-title":"Matrix metalloproteinases as biomarkers of atherosclerotic plaque instability","volume":"21","author":"Olejarz","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2025032523070085100_fcaf097-B83","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijcard.2015.03.054","article-title":"Early matrix metalloproteinase-12 inhibition worsens post-myocardial infarction cardiac dysfunction by delaying inflammation resolution","volume":"185","author":"Iyer","year":"2015","journal-title":"Int J Cardiol"},{"issue":"1","key":"2025032523070085100_fcaf097-B84","doi-asserted-by":"crossref","first-page":"21314","DOI":"10.1038\/s41598-020-78341-y","article-title":"The matrix metalloproteinase inhibitor marimastat inhibits seizures in a model of kainic acid-induced status epilepticus","volume":"10","author":"Pijet","year":"2020","journal-title":"Sci Rep"},{"issue":"1","key":"2025032523070085100_fcaf097-B85","doi-asserted-by":"crossref","first-page":"7817","DOI":"10.1038\/s41467-023-43575-7","article-title":"Plasma proteomic profiles predict individual future health risk","volume":"14","author":"You","year":"2023","journal-title":"Nat Communs"},{"issue":"1","key":"2025032523070085100_fcaf097-B86","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/s41467-019-14161-7","article-title":"Neurology-related protein biomarkers are associated with cognitive ability and brain volume in older age","volume":"11","author":"Harris","year":"2020","journal-title":"Nat Commun"},{"issue":"4","key":"2025032523070085100_fcaf097-B87","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1007\/s11357-023-00764-y","article-title":"Plasma levels of neurology-related proteins are associated with cognitive performance in an older population with overweight\/obesity and metabolic syndrome","volume":"45","author":"Llaurador-Coll","year":"2023","journal-title":"GeroScience"},{"issue":"7","key":"2025032523070085100_fcaf097-B88","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1002\/alz.13895","article-title":"Considerations for the use of the informant questionnaire on cognitive decline in the elderly (IQCODE) in cross-country comparisons of cognitive aging and dementia","volume":"20","author":"Nichols","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"10","key":"2025032523070085100_fcaf097-B89","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1001\/jamaneurol.2022.2967","article-title":"The ATN framework\u2014Moving preclinical Alzheimer disease to clinical relevance","volume":"79","author":"van der Flier","year":"2022","journal-title":"JAMA Neurol"},{"issue":"23","key":"2025032523070085100_fcaf097-B90","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1001\/jama.292.23.2901","article-title":"Mixed dementia: Emerging concepts and therapeutic implications","volume":"292","author":"Langa","year":"2004","journal-title":"JAMA"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcaf097\/62244333\/fcaf097.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/2\/fcaf097\/62244333\/fcaf097.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/2\/fcaf097\/62244333\/fcaf097.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:08:07Z","timestamp":1743221287000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcaf097\/8051152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":90,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcaf097","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"fcaf097"}}