{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:16:21Z","timestamp":1777392981443,"version":"3.51.4"},"reference-count":53,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,7,16]]},"abstract":"<jats:p>Background: The identification of biomarkers for different dementias in plasma and cerebrospinal fluid (CSF) has made substantial progress. However, they are observational studies, and there remains a lack of research on dementias with low incidence rates. Objective: We performed a comprehensive Mendelian randomization to identify potential biomarkers for different dementia type. Methods: The summary-level datasets encompassed 734 plasma and 154 cerebrospinal fluid proteins sourced from recently published genome-wide association studies (GWAS). Summary statistics for different dementias, including any dementia (refering to any type of dementia symptoms, 218,792 samples), Alzheimer\u2019s disease (AD, 63,926 samples), vascular dementia (212,389 samples), frontotemporal dementia (3,024 samples), dementia with Lewy bodies (DLB, 6,618 samples), and dementia in Parkinson\u2019s disease (216,895 samples), were collected from large GWAS. The primary method is inverse variance weighting, with additional sensitivity analyses conducted to ensure the robustness of the findings. Results: The molecules released into CSF, namely APOE2 for any dementia, APOE2 and Siglec-3 for AD, APOE2 for vascular dementia, and APOE2 for DLB, might be potential biomarkers. CD33 for AD and SNCA for DLB in plasma could be promising biomarkers. Conclusions: This is the first study to integrate plasma and CSF proteins to identify potential biomarkers for different dementias.<\/jats:p>","DOI":"10.3233\/jad-240260","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T12:51:43Z","timestamp":1718110303000},"page":"603-611","source":"Crossref","is-referenced-by-count":3,"title":["Potential Biomarkers in Cerebrospinal Fluid and Plasma for Dementia"],"prefix":"10.1177","volume":"100","author":[{"given":"Qiang","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Urology, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanyuan","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"You","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-240260_ref1","first-page":"CD012820","article-title":"Cannabinoids for the treatment of dementia","volume":"9","author":"Bosnjak Kuharic","year":"2021","journal-title":"Cochrane Database Syst Rev"},{"key":"10.3233\/JAD-240260_ref2","doi-asserted-by":"crossref","unstructured":"(2022) 2022 Alzheimer\u2019s disease facts and figures. Alzheimers Dement 18, 700\u2013789.","DOI":"10.1002\/alz.12638"},{"key":"10.3233\/JAD-240260_ref3","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Collaborators GBDDF","year":"2022","journal-title":"Lancet Public Health"},{"key":"10.3233\/JAD-240260_ref4","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"},{"key":"10.3233\/JAD-240260_ref5","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jalz.2015.10.009","article-title":"Comparative analysis of cerebrospinal fluid biomarkers in the differential diagnosis of neurodegenerative dementia","volume":"12","author":"Llorens","year":"2016","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240260_ref6","doi-asserted-by":"crossref","first-page":"e12285","DOI":"10.1002\/dad2.12285","article-title":"Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia","volume":"14","author":"Thijssen","year":"2022","journal-title":"Alzheimers Dement (Amst)"},{"key":"10.3233\/JAD-240260_ref7","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"10.3233\/JAD-240260_ref8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ije\/dyg070","article-title":"\u2018Mendelian randomization\u2019: Can genetic epidemiology contribute to understanding environmental determinants of disease?","volume":"32","author":"Smith","year":"2003","journal-title":"Int J Epidemiol"},{"key":"10.3233\/JAD-240260_ref9","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1177\/0271678X231169838","article-title":"Genetic insights into the risk of metabolic syndrome and its components on stroke and its subtypes: Bidirectional Mendelian randomization","volume":"43","author":"He","year":"2023","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-240260_ref10","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/s41588-020-0682-6","article-title":"Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases","volume":"52","author":"Zheng","year":"2020","journal-title":"Nat Genet"},{"key":"10.3233\/JAD-240260_ref11","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41586-018-0175-2","article-title":"Genomic atlas of the human plasma proteome","volume":"558","author":"Sun","year":"2018","journal-title":"Nature"},{"key":"10.3233\/JAD-240260_ref12","doi-asserted-by":"crossref","first-page":"14357","DOI":"10.1038\/ncomms14357","article-title":"Connecting genetic risk to disease end points through the human blood plasma proteome","volume":"8","author":"Suhre","year":"2017","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-240260_ref13","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1038\/s41467-018-05512-x","article-title":"Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease","volume":"9","author":"Yao","year":"2018","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-240260_ref14","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1126\/science.aaq1327","article-title":"Co-regulatory networks of human serum proteins link genetics to disease","volume":"361","author":"Emilsson","year":"2018","journal-title":"Science"},{"key":"10.3233\/JAD-240260_ref15","doi-asserted-by":"crossref","first-page":"e1006706","DOI":"10.1371\/journal.pgen.1006706","article-title":"Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease","volume":"13","author":"Folkersen","year":"2017","journal-title":"PLoS Genet"},{"key":"10.3233\/JAD-240260_ref16","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/s41593-021-00886-6","article-title":"Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders","volume":"24","author":"Yang","year":"2021","journal-title":"Nat Neurosci"},{"key":"10.3233\/JAD-240260_ref17","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing","volume":"51","author":"Kunkle","year":"2019","journal-title":"Nat Genet"},{"key":"10.3233\/JAD-240260_ref18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/ng.536","article-title":"Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions","volume":"42","author":"Van Deerlin","year":"2010","journal-title":"Nat Genet"},{"key":"10.3233\/JAD-240260_ref19","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41588-021-00785-3","article-title":"Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture","volume":"53","author":"Chia","year":"2021","journal-title":"Nat Genet"},{"key":"10.3233\/JAD-240260_ref20","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"10.3233\/JAD-240260_ref21","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1038\/s41380-022-01507-9","article-title":"Identifying causal genes for depression via integration of the proteome and transcriptome from brain and blood","volume":"27","author":"Deng","year":"2022","journal-title":"Mol Psychiatry"},{"key":"10.3233\/JAD-240260_ref22","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: An expanded tool for searching human genotype-phenotype associations","volume":"35","author":"Kamat","year":"2019","journal-title":"Bioinformatics"},{"key":"10.3233\/JAD-240260_ref23","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.1","article-title":"Guidelines for performing Mendelian randomization investigations: Update for summer 2023","volume":"4","author":"Burgess","year":"2019","journal-title":"Wellcome Open Res"},{"key":"10.3233\/JAD-240260_ref24","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3233\/ADR-230058","article-title":"Identifying suitable targets for Alzheimer\u2019s disease and other eight common neurological disorders using the human plasma proteome: A Mendelian randomization study","volume":"7","author":"Wei","year":"2023","journal-title":"J Alzheimers Dis Rep"},{"key":"10.3233\/JAD-240260_ref25","doi-asserted-by":"crossref","first-page":"653334","DOI":"10.3389\/fnagi.2021.653334","article-title":"Role of neuron and glia in Alzheimer\u2019s disease and associated vascular dysfunction","volume":"13","author":"Bandyopadhyay","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-240260_ref26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00401-024-02696-z","article-title":"The contribution of beta-amyloid, Tau and alpha-synuclein to blood-brain barrier damage in neurodegenerative disorders","volume":"147","author":"Wu","year":"2024","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-240260_ref27","doi-asserted-by":"crossref","first-page":"5907","DOI":"10.1038\/s41467-021-26066-5","article-title":"Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption","volume":"12","author":"Pediaditakis","year":"2021","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-240260_ref28","doi-asserted-by":"crossref","first-page":"17314","DOI":"10.1038\/s41598-022-20261-0","article-title":"Pericytes take up and degrade alpha-synuclein but succumb to apoptosis under cellular stress","volume":"12","author":"Stevenson","year":"2022","journal-title":"Sci Rep"},{"key":"10.3233\/JAD-240260_ref29","doi-asserted-by":"crossref","first-page":"e50976","DOI":"10.1371\/journal.pone.0050976","article-title":"Expression of novel Alzheimer\u2019s disease risk genes in control and Alzheimer\u2019s disease brains","volume":"7","author":"Karch","year":"2012","journal-title":"PLoS One"},{"key":"10.3233\/JAD-240260_ref30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.21037\/atm.2018.04.21","article-title":"Meta-analysis of the association between CD33 and Alzheimer\u2019s disease","volume":"6","author":"Jiang","year":"2018","journal-title":"Ann Transl Med"},{"key":"10.3233\/JAD-240260_ref31","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1159\/000518820","article-title":"CD33 mRNA has elevated expression levels in the leukocytes of peripheral blood in patients with late-onset Alzheimer\u2019s disease","volume":"68","author":"Heidari","year":"2022","journal-title":"Gerontology"},{"key":"10.3233\/JAD-240260_ref32","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neulet.2014.01.004","article-title":"Decreased expression of CD33 in peripheral mononuclear cells of Alzheimer\u2019s disease patients","volume":"563","author":"Hu","year":"2014","journal-title":"Neurosci Lett"},{"key":"10.3233\/JAD-240260_ref33","doi-asserted-by":"crossref","first-page":"7042","DOI":"10.1038\/s41467-021-27387-1","article-title":"Mapping the serum proteome to neurological diseases using whole genome sequencing","volume":"12","author":"Png","year":"2021","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-240260_ref34","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41398-022-02205-4","article-title":"Peripheral level of CD33 and Alzheimer\u2019s disease: A bidirectional two-sample Mendelian randomization study","volume":"12","author":"Gu","year":"2022","journal-title":"Transl Psychiatry"},{"key":"10.3233\/JAD-240260_ref35","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1212\/WNL.0000000000001279","article-title":"Inflammatory biomarkers, cerebral microbleeds, and small vessel disease: Framingham Heart Study","volume":"84","author":"Shoamanesh","year":"2015","journal-title":"Neurology"},{"key":"10.3233\/JAD-240260_ref36","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jns.2008.05.020","article-title":"Markers of endothelial dysfunction in older subjects with late onset Alzheimer\u2019s disease or vascular dementia","volume":"272","author":"Zuliani","year":"2008","journal-title":"J Neurol Sci"},{"key":"10.3233\/JAD-240260_ref37","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1001\/archneur.61.5.668","article-title":"Inflammatory proteins in plasma and the risk of dementia: The rotterdam study","volume":"61","author":"Engelhart","year":"2004","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-240260_ref38","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1002\/alz.12974","article-title":"Placental growth factor as a sensitive biomarker for vascular cognitive impairment","volume":"19","author":"Hinman","year":"2023","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240260_ref39","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41582-023-00884-1","article-title":"Molecular biomarkers for vascular cognitive impairment and dementia","volume":"19","author":"Hosoki","year":"2023","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JAD-240260_ref40","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1161\/01.STR.0000127420.10990.76","article-title":"Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease","volume":"35","author":"Adair","year":"2004","journal-title":"Stroke"},{"key":"10.3233\/JAD-240260_ref41","doi-asserted-by":"crossref","first-page":"717344","DOI":"10.3389\/fnagi.2021.717344","article-title":"Inflammatory biomarkers aid in diagnosis of dementia","volume":"13","author":"Erhardt","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-240260_ref42","first-page":"100216","article-title":"Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis","volume":"6","author":"Hansra","year":"2024","journal-title":"Cereb Circ Cogn Behav"},{"key":"10.3233\/JAD-240260_ref43","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3233\/JAD-200168","article-title":"Cerebrospinal fluid\/plasma albumin ratio as a biomarker for blood-brain barrier impairment across neurodegenerative dementias","volume":"75","author":"Musaeus","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-240260_ref44","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/jcbfm.2013.76","article-title":"The APOE varepsilon4\/varepsilon4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer\u2019s disease patients","volume":"33","author":"Hultman","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-240260_ref45","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nature11087","article-title":"Apolipoprotein E controls cerebrovascular integrity via cyclophilin A","volume":"485","author":"Bell","year":"2012","journal-title":"Nature"},{"key":"10.3233\/JAD-240260_ref46","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"10.3233\/JAD-240260_ref47","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat Med"},{"key":"10.3233\/JAD-240260_ref48","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","article-title":"APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline","volume":"581","author":"Montagne","year":"2020","journal-title":"Nature"},{"key":"10.3233\/JAD-240260_ref49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.neulet.2015.09.025","article-title":"Shedding of soluble platelet-derived growth factor receptor-beta from human brain pericytes","volume":"607","author":"Sagare","year":"2015","journal-title":"Neurosci Lett"},{"key":"10.3233\/JAD-240260_ref50","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1002\/alz.12165","article-title":"APOE and dementia - resequencing and genotyping in 105,597 individuals","volume":"16","author":"Rasmussen","year":"2020","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-240260_ref51","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Serrano-Pozo","year":"2021","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-240260_ref52","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3233\/JAD-143102","article-title":"Genetics of vascular dementia: Systematic review and meta-analysis","volume":"46","author":"Sun","year":"2015","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-240260_ref53","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41586-023-06957-x","article-title":"Genomic data in the All of Us Research Program","volume":"627","author":"All of Us Research Program Genomics Investigators","year":"2024","journal-title":"Nature"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-240260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:58:32Z","timestamp":1777370312000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-240260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":53,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-240260","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,16]]}}}