{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T15:10:19Z","timestamp":1774883419987,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,19]]},"group-title":"Epidemiology","reference-count":121,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Alzheimer\u2019s disease and related dementias (ADRD) pose a growing global health challenge, with early detection critical to slowing cognitive decline and prevent ADRD. We analyzed high-throughput plasma proteomics in 2,460 cognitively healthy adults from the English Longitudinal Study of Ageing (ELSA) to identify proteins linked to 15-year cognitive trajectories, including verbal fluency, episodic memory, and orientation. Mixed-effect linear models revealed 34 proteins associated with faster orientation decline and 18 with accelerated episodic memory decline. Enrichment analyses implicate extracellular matrix remodeling, immune signaling, apoptosis, and lysosomal-autophagic pathways in cognitive deterioration. Subgroup analyses showed sex-specific effects, highlighting heterogeneity in proteomics signatures in cognitive aging. Notably, ten identified proteins are targets of drugs under clinical investigation, suggesting opportunities for therapeutic repurposing. These findings define a plasma proteomic signature associated with decline in domain-specific cognitive functions, offering promising biomarkers and druggable targets to prevent or slow age-related cognitive decline.<\/jats:p>","DOI":"10.64898\/2026.03.19.26348791","type":"posted-content","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:11:11Z","timestamp":1773965471000},"source":"Crossref","is-referenced-by-count":0,"title":["Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing"],"prefix":"10.64898","author":[{"given":"Jessica","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London, London, UK"},{"name":"Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"},{"name":"George Institute for Global Health, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikaela","family":"Bloomberg","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaun","family":"Scholes","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinran","family":"Hao","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7651-8998","authenticated-orcid":false,"given":"Dervis A.","family":"Salih","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Zaninotto","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Steptoe","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University College London, London, UK"},{"name":"Department of Behavioural Science and Health, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026033007401327000_2026.03.19.26348791v3.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00064-X"},{"key":"2026033007401327000_2026.03.19.26348791v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"issue":"3","key":"2026033007401327000_2026.03.19.26348791v3.3","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1002\/alz.13583","article-title":"Blood\u25a1based biomarkers for Alzheimer\u2019s disease and cognitive function from mid\u25a1to late life","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026033007401327000_2026.03.19.26348791v3.4","unstructured":"Organization, W.H ., Risk reduction of cognitive decline and dementia: WHO guidelines. 2019: World Health Organization."},{"key":"2026033007401327000_2026.03.19.26348791v3.5","doi-asserted-by":"crossref","unstructured":"Sun, B.B. , K. Suhre , and B.W. Gibson , Promises and challenges of populational proteomics in health and disease. Molecular & Cellular Proteomics, 2024: p. 100786.","DOI":"10.1016\/j.mcpro.2024.100786"},{"key":"2026033007401327000_2026.03.19.26348791v3.6","doi-asserted-by":"crossref","unstructured":"Gong, J. , et al., Unraveling the role of plasma proteins in dementia: insights from two cohort studies in the UK, with causal evidence from Mendelian randomization (in press). Brain Communications, 2025: p. 2024.06.04.24308415.","DOI":"10.1101\/2024.06.04.24308415"},{"issue":"4","key":"2026033007401327000_2026.03.19.26348791v3.7","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/alz.12419","article-title":"Plasma proteins, cognitive decline, and 20\u25a1year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies","volume":"18","year":"2022","journal-title":"Alzheimer\u2019s & dementia"},{"key":"2026033007401327000_2026.03.19.26348791v3.8","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf5681"},{"issue":"5","key":"2026033007401327000_2026.03.19.26348791v3.9","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","year":"2021","journal-title":"Nature Aging"},{"issue":"2","key":"2026033007401327000_2026.03.19.26348791v3.10","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","year":"2024","journal-title":"Nature Aging"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13195-022-01063-y","article-title":"Association of the inflammation-related proteome with dementia development at older age: results from a large, prospective, population-based cohort study","volume":"14","year":"2022","journal-title":"Alzheimer\u2019s Research & Therapy"},{"key":"2026033007401327000_2026.03.19.26348791v3.12","doi-asserted-by":"crossref","unstructured":"Deng, Y.-T. , et al., Atlas of the plasma proteome in health and disease in 53,026 adults. Cell, 2024.","DOI":"10.1016\/j.cell.2024.10.045"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.13","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","year":"2020","journal-title":"Nature Communications"},{"issue":"4","key":"2026033007401327000_2026.03.19.26348791v3.14","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","year":"2023","journal-title":"GeroScience"},{"issue":"10","key":"2026033007401327000_2026.03.19.26348791v3.15","doi-asserted-by":"crossref","first-page":"e13955","DOI":"10.1111\/acel.13955","article-title":"Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort","volume":"22","year":"2023","journal-title":"Aging cell"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1186\/s12888-024-06054-x","article-title":"Exploring the relationship between lipid metabolism and cognition in individuals living with stable-phase Schizophrenia: a small cross-sectional study using Olink proteomics analysis","volume":"24","year":"2024","journal-title":"BMC psychiatry"},{"key":"2026033007401327000_2026.03.19.26348791v3.17","first-page":"e12018","article-title":"Plasma proteomic signatures predict dementia and cognitive impairment","volume":"6","year":"2020","journal-title":"Alzheimers. Dement"},{"key":"2026033007401327000_2026.03.19.26348791v3.18","doi-asserted-by":"crossref","first-page":"e079341","DOI":"10.1002\/alz.079341","article-title":"Discovery\u25a1based proteomics identifies plasma proteins that predict longitudinal cognitive decline in older adults over a 7\u25a1year follow\u25a1up period","volume":"19","year":"2023","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"9","key":"2026033007401327000_2026.03.19.26348791v3.19","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/s43587-024-00682-4","article-title":"Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline","volume":"4","year":"2024","journal-title":"Nature Aging"},{"issue":"4","key":"2026033007401327000_2026.03.19.26348791v3.20","doi-asserted-by":"crossref","first-page":"fcac155","DOI":"10.1093\/braincomms\/fcac155","article-title":"Plasma biomarkers for prognosis of cognitive decline in patients with mild cognitive impairment","volume":"4","year":"2022","journal-title":"Brain Communications"},{"key":"2026033007401327000_2026.03.19.26348791v3.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-01975-7"},{"issue":"4","key":"2026033007401327000_2026.03.19.26348791v3.22","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/jnnp-2024-333819","article-title":"Neuropsychiatric symptoms in cognitive decline and Alzheimer\u2019s disease: biomarker discovery using plasma proteomics. Journal of Neurology","volume":"96","year":"2025","journal-title":"Neurosurgery & Psychiatry"},{"issue":"2","key":"2026033007401327000_2026.03.19.26348791v3.23","doi-asserted-by":"crossref","first-page":"e14577","DOI":"10.1002\/alz.14577","article-title":"Plasma proteomics for cognitive decline and dementia\u2014A Southeast Asian cohort study","volume":"21","year":"2025","journal-title":"Alzheimer\u2019s & dementia"},{"issue":"6","key":"2026033007401327000_2026.03.19.26348791v3.24","doi-asserted-by":"crossref","first-page":"e70276","DOI":"10.1002\/alz.70276","article-title":"LC\u25a1MS\/MS proteomics identifies plasma proteins related to cognition over 9\u25a1year follow\u25a1up","volume":"21","year":"2025","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026033007401327000_2026.03.19.26348791v3.25","unstructured":"Duggan, M.R. , et al., Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline. Nature Aging, 2024: p. 1\u201316."},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.26","first-page":"e12018","article-title":"Plasma proteomic signatures predict dementia and cognitive impairment","volume":"6","year":"2020","journal-title":"Alzheimer\u2019s & Dementia: Translational Research & Clinical Interventions"},{"key":"2026033007401327000_2026.03.19.26348791v3.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001679118"},{"issue":"9","key":"2026033007401327000_2026.03.19.26348791v3.28","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1002\/art.38727","article-title":"Brief report: involvement of TNFRSF11A molecular defects in autoinflammatory disorders","volume":"66","year":"2014","journal-title":"Arthritis & Rheumatology"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.29","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41420-023-01544-5","article-title":"Dysregulation of a lncRNA within the TNFRSF10A locus activates cell death pathways","volume":"9","year":"2023","journal-title":"Cell Death Discovery"},{"key":"2026033007401327000_2026.03.19.26348791v3.30","doi-asserted-by":"publisher","DOI":"10.1038\/nature17630"},{"issue":"5","key":"2026033007401327000_2026.03.19.26348791v3.31","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41590-021-00913-5","article-title":"Microglia use TAM receptors to detect and engulf amyloid \u03b2 plaques","volume":"22","year":"2021","journal-title":"Nature immunology"},{"issue":"2","key":"2026033007401327000_2026.03.19.26348791v3.32","doi-asserted-by":"crossref","first-page":"e70341","DOI":"10.1096\/fj.202402183RR","article-title":"Novel inflammatory markers in intracerebral hemorrhage: Results from Olink proteomics analysis","volume":"39","year":"2025","journal-title":"The FASEB Journal"},{"key":"2026033007401327000_2026.03.19.26348791v3.33","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1210-1248"},{"key":"2026033007401327000_2026.03.19.26348791v3.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.03.004"},{"key":"2026033007401327000_2026.03.19.26348791v3.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.10.015"},{"issue":"4","key":"2026033007401327000_2026.03.19.26348791v3.36","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","year":"2015","journal-title":"The Lancet Neurology"},{"issue":"5","key":"2026033007401327000_2026.03.19.26348791v3.37","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","year":"2017","journal-title":"Journal of neurotrauma"},{"key":"2026033007401327000_2026.03.19.26348791v3.38","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abg9922"},{"key":"2026033007401327000_2026.03.19.26348791v3.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.06.030"},{"key":"2026033007401327000_2026.03.19.26348791v3.40","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320106"},{"issue":"3","key":"2026033007401327000_2026.03.19.26348791v3.41","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","year":"2019","journal-title":"JAMA neurology"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.42","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","year":"2021","journal-title":"Nature communications"},{"key":"2026033007401327000_2026.03.19.26348791v3.43","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24954"},{"key":"2026033007401327000_2026.03.19.26348791v3.44","doi-asserted-by":"crossref","first-page":"581767","DOI":"10.3389\/fnagi.2020.581767","article-title":"Axonal degeneration in AD: the contribution of A\u03b2 and Tau","volume":"12","year":"2020","journal-title":"Frontiers in Aging Neuroscience"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.45","first-page":"e200322","article-title":"Proteomics reveals age as major modifier of inflammatory CSF signatures in multiple sclerosis","volume":"12","year":"2024","journal-title":"Neurology: Neuroimmunology & Neuroinflammation"},{"issue":"8","key":"2026033007401327000_2026.03.19.26348791v3.46","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1093\/brain\/awad070","article-title":"Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis","volume":"146","year":"2023","journal-title":"Brain"},{"issue":"2","key":"2026033007401327000_2026.03.19.26348791v3.47","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/acn3.52250","article-title":"APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia","volume":"12","year":"2025","journal-title":"Annals of Clinical and Translational Neurology"},{"key":"2026033007401327000_2026.03.19.26348791v3.48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47650.001"},{"key":"2026033007401327000_2026.03.19.26348791v3.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2617-16.2017"},{"key":"2026033007401327000_2026.03.19.26348791v3.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.032"},{"key":"2026033007401327000_2026.03.19.26348791v3.51","doi-asserted-by":"crossref","unstructured":"Hartz, A.M. , et al., Amyloid-\u03b2 contributes to blood\u2013brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy . Stroke, 2012.","DOI":"10.1161\/STROKEAHA.111.627562"},{"issue":"6","key":"2026033007401327000_2026.03.19.26348791v3.52","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1093\/brain\/awae034","article-title":"Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer\u2019s disease","volume":"147","year":"2024","journal-title":"Brain"},{"key":"2026033007401327000_2026.03.19.26348791v3.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.02.062"},{"key":"2026033007401327000_2026.03.19.26348791v3.54","doi-asserted-by":"publisher","DOI":"10.3109\/07853891003652542"},{"issue":"13","key":"2026033007401327000_2026.03.19.26348791v3.55","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1212\/WNL.0000000000000820","article-title":"NT-proBNP, blood pressure, and cognitive decline in the oldest old: The Leiden 85-plus Study","volume":"83","year":"2014","journal-title":"Neurology"},{"issue":"7","key":"2026033007401327000_2026.03.19.26348791v3.56","doi-asserted-by":"crossref","first-page":"670. e1","DOI":"10.1016\/j.amjmed.2011.02.027","article-title":"Elevated natriuretic peptide levels and cognitive function in community-dwelling older adults","volume":"124","year":"2011","journal-title":"The American Journal of Medicine"},{"key":"2026033007401327000_2026.03.19.26348791v3.57","unstructured":"Lu, X.-D. , Y.-R. Liu , and Z.-Y. Zhang , Matrilin-3 alleviates extracellular matrix degradation of nucleus pulposus cells via induction of IL-1 receptor antagonist. European Review for Medical & Pharmacological Sciences, 2020. 24(10)."},{"key":"2026033007401327000_2026.03.19.26348791v3.58","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23869"},{"issue":"21","key":"2026033007401327000_2026.03.19.26348791v3.59","doi-asserted-by":"crossref","first-page":"6376","DOI":"10.7150\/jca.46309","article-title":"PRELP has prognostic value and regulates cell proliferation and migration in hepatocellular carcinoma","volume":"11","year":"2020","journal-title":"Journal of Cancer"},{"key":"2026033007401327000_2026.03.19.26348791v3.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.05.004"},{"key":"2026033007401327000_2026.03.19.26348791v3.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.05.020"},{"key":"2026033007401327000_2026.03.19.26348791v3.62","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105972200"},{"key":"2026033007401327000_2026.03.19.26348791v3.63","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160604"},{"key":"2026033007401327000_2026.03.19.26348791v3.64","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2164-7"},{"issue":"19","key":"2026033007401327000_2026.03.19.26348791v3.65","doi-asserted-by":"crossref","first-page":"11625","DOI":"10.3390\/ijms231911625","article-title":"TRAIL-R deficient mice are protected from neurotoxic effects of amyloid-\u03b2","volume":"23","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"key":"2026033007401327000_2026.03.19.26348791v3.66","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fncel.2019.00227","article-title":"Wnt signaling deregulation in the aging and Alzheimer\u2019s brain","volume":"13","year":"2019","journal-title":"Frontiers in cellular neuroscience"},{"key":"2026033007401327000_2026.03.19.26348791v3.67","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjt051"},{"issue":"8","key":"2026033007401327000_2026.03.19.26348791v3.68","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1755-5949.2012.00340.x","article-title":"Tight junction in blood\u25a1brain barrier: an overview of structure, regulation, and regulator substances","volume":"18","year":"2012","journal-title":"CNS neuroscience & therapeutics"},{"issue":"12","key":"2026033007401327000_2026.03.19.26348791v3.69","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.jalz.2018.06.2857","article-title":"Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults","volume":"14","year":"2018","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"6","key":"2026033007401327000_2026.03.19.26348791v3.70","doi-asserted-by":"crossref","first-page":"H924","DOI":"10.1152\/ajpheart.00616.2021","article-title":"Microvascular dysfunction and neurovascular uncoupling are exacerbated in peripheral artery disease, increasing the risk of cognitive decline in older adults","volume":"322","year":"2022","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"2026033007401327000_2026.03.19.26348791v3.71","doi-asserted-by":"crossref","first-page":"1224525","DOI":"10.3389\/fnagi.2023.1224525","article-title":"Altered neurovascular coupling in patients with vascular cognitive impairment: a combined ASL-fMRI analysis","volume":"15","year":"2023","journal-title":"Frontiers in Aging Neuroscience"},{"key":"2026033007401327000_2026.03.19.26348791v3.72","doi-asserted-by":"publisher","DOI":"10.1007\/s004269900007"},{"key":"2026033007401327000_2026.03.19.26348791v3.73","first-page":"38","article-title":"Cognitive functions of the posterior parietal cortex: top-down and bottom-up attentional control","volume":"6","year":"2012","journal-title":"Frontiers in integrative neuroscience"},{"issue":"9","key":"2026033007401327000_2026.03.19.26348791v3.74","doi-asserted-by":"crossref","first-page":"898","DOI":"10.3390\/brainsci14090898","article-title":"Spatial orientation assessment in the elderly: a comprehensive review of current tests","volume":"14","year":"2024","journal-title":"Brain Sciences"},{"issue":"6","key":"2026033007401327000_2026.03.19.26348791v3.75","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.14283\/jpad.2024.107","article-title":"Blood Cathepsins on the Risk of Alzheimer\u2019s Disease and Related Pathological Biomarkers: Results from Observational Cohort and Mendelian Randomization Study","volume":"11","year":"2024","journal-title":"The Journal of Prevention of Alzheimer\u2019s Disease"},{"key":"2026033007401327000_2026.03.19.26348791v3.76","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103645200"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.77","doi-asserted-by":"crossref","first-page":"21019","DOI":"10.1038\/srep21019","article-title":"Transferrin receptor controls AMPA receptor trafficking efficiency and synaptic plasticity","volume":"6","year":"2016","journal-title":"Scientific reports"},{"key":"2026033007401327000_2026.03.19.26348791v3.78","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-23-09026.1997"},{"key":"2026033007401327000_2026.03.19.26348791v3.79","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1994.tb00998.x"},{"issue":"9","key":"2026033007401327000_2026.03.19.26348791v3.80","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1007\/s12035-022-02929-w","article-title":"Hippocampal iron accumulation impairs synapses and memory via suppressing furin expression and downregulating BDNF maturation","volume":"59","year":"2022","journal-title":"Molecular Neurobiology"},{"key":"2026033007401327000_2026.03.19.26348791v3.81","doi-asserted-by":"publisher","DOI":"10.3945\/jn.108.096354"},{"key":"2026033007401327000_2026.03.19.26348791v3.82","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00193.2007"},{"key":"2026033007401327000_2026.03.19.26348791v3.83","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01107.2006"},{"key":"2026033007401327000_2026.03.19.26348791v3.84","unstructured":"Oh, H.S.-H. , et al., Plasma proteomics links brain and immune system aging with healthspan and longevity. Nature Medicine, 2025: p. 1\u20139."},{"key":"2026033007401327000_2026.03.19.26348791v3.85","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"2026033007401327000_2026.03.19.26348791v3.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2011.11.012"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.87","first-page":"e70037","article-title":"Data\u25a1driven discovery of associations between prescribed drugs and dementia risk: A systematic review","volume":"11","year":"2025","journal-title":"Alzheimer\u2019s & Dementia: Translational Research & Clinical Interventions"},{"issue":"11","key":"2026033007401327000_2026.03.19.26348791v3.88","doi-asserted-by":"crossref","first-page":"e70079","DOI":"10.1111\/cns.70079","article-title":"Endothelial Dysfunctions in Blood\u2013Brain Barrier Breakdown in Alzheimer\u2019s Disease: From Mechanisms to Potential Therapies","volume":"30","year":"2024","journal-title":"CNS Neuroscience & Therapeutics"},{"issue":"8","key":"2026033007401327000_2026.03.19.26348791v3.89","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1161\/STROKEAHA.121.034362","article-title":"Aflibercept, a VEGF (vascular endothelial growth factor)-trap, reduces vascular permeability and stroke-induced brain swelling in obese mice","volume":"52","year":"2021","journal-title":"Stroke"},{"key":"2026033007401327000_2026.03.19.26348791v3.90","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.3389\/fimmu.2018.02551","article-title":"Mechanisms of NK cell activation and clinical activity of the therapeutic SLAMF7 antibody, elotuzumab in multiple myeloma","volume":"9","year":"2018","journal-title":"Frontiers in immunology"},{"key":"2026033007401327000_2026.03.19.26348791v3.91","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.44.1055"},{"key":"2026033007401327000_2026.03.19.26348791v3.92","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2006.11.013"},{"key":"2026033007401327000_2026.03.19.26348791v3.93","doi-asserted-by":"publisher","DOI":"10.1080\/13803395.2017.1342772"},{"issue":"2","key":"2026033007401327000_2026.03.19.26348791v3.94","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1017\/S0140525X06319036","article-title":"Working memory, executive function, and general fluid intelligence are not the same","volume":"29","year":"2006","journal-title":"Behavioral and Brain Sciences"},{"key":"2026033007401327000_2026.03.19.26348791v3.95","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2017-210228"},{"key":"2026033007401327000_2026.03.19.26348791v3.96","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"2026033007401327000_2026.03.19.26348791v3.97","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4541-7"},{"key":"2026033007401327000_2026.03.19.26348791v3.98","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2017-210116"},{"key":"2026033007401327000_2026.03.19.26348791v3.99","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys168"},{"issue":"4","key":"2026033007401327000_2026.03.19.26348791v3.100","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jalz.2007.07.013","article-title":"Mild cognitive impairment and cognitive impairment, no dementia: Part A, concept and diagnosis","volume":"3","year":"2007","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026033007401327000_2026.03.19.26348791v3.101","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-025309"},{"key":"2026033007401327000_2026.03.19.26348791v3.102","doi-asserted-by":"publisher","DOI":"10.1007\/BF01537606"},{"issue":"7","key":"2026033007401327000_2026.03.19.26348791v3.103","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","year":"2020","journal-title":"Journal of the American Geriatrics Society"},{"key":"2026033007401327000_2026.03.19.26348791v3.104","first-page":"1","article-title":"mice: Multivariate imputation by chained equations in R","volume":"45","year":"2011","journal-title":"Journal of statistical software"},{"issue":"19","key":"2026033007401327000_2026.03.19.26348791v3.105","first-page":"1","article-title":"A comparison of multiple imputation methods for data with missing values","volume":"10","year":"2017","journal-title":"Indian Journal of Science and Technology"},{"issue":"1","key":"2026033007401327000_2026.03.19.26348791v3.106","first-page":"2","volume":"12","year":"2015","journal-title":"Package \u2018lme4\u2019. convergence"},{"key":"2026033007401327000_2026.03.19.26348791v3.107","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v082.i13"},{"issue":"26","key":"2026033007401327000_2026.03.19.26348791v3.108","doi-asserted-by":"crossref","first-page":"772","DOI":"10.21105\/joss.00772","article-title":", ggeffects: Tidy data frames of marginal effects from regression models","volume":"3","year":"2018","journal-title":"Journal of open source software"},{"key":"2026033007401327000_2026.03.19.26348791v3.109","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"2026033007401327000_2026.03.19.26348791v3.110","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh036"},{"key":"2026033007401327000_2026.03.19.26348791v3.111","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"2026033007401327000_2026.03.19.26348791v3.112","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1028"},{"key":"2026033007401327000_2026.03.19.26348791v3.113","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-1"},{"key":"2026033007401327000_2026.03.19.26348791v3.114","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"2026033007401327000_2026.03.19.26348791v3.115","unstructured":"Hagberg, A. , P.J. Swart , and D.A. Schult , Exploring network structure, dynamics, and function using NetworkX. 2008, Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)."},{"issue":"3","key":"2026033007401327000_2026.03.19.26348791v3.116","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1093\/brain\/awae339","article-title":"Human longevity and Alzheimer\u2019s disease variants act via microglia and oligodendrocyte gene networks","volume":"148","year":"2025","journal-title":"Brain"},{"key":"2026033007401327000_2026.03.19.26348791v3.117","doi-asserted-by":"publisher","DOI":"10.1126\/science.1262110"},{"key":"2026033007401327000_2026.03.19.26348791v3.118","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01128-z"},{"key":"2026033007401327000_2026.03.19.26348791v3.119","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1070"},{"key":"2026033007401327000_2026.03.19.26348791v3.120","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1055"},{"key":"2026033007401327000_2026.03.19.26348791v3.121","unstructured":"Allaire, J. , et al., Package \u2018networkD3\u2019. D3 JavaScript network graphs from R, 2017."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.19.26348791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:40:26Z","timestamp":1774881626000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.03.19.26348791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":121,"URL":"https:\/\/doi.org\/10.64898\/2026.03.19.26348791","relation":{},"subject":[],"published":{"date-parts":[[2026,3,19]]},"subtype":"preprint"}}