{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:06:44Z","timestamp":1787170004451,"version":"build-2736575974"},"reference-count":70,"publisher":"The Royal Society","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UKRI\/NIHR Multimorbidity Fund Mechanism and Therapeutics Research Collaborative","award":["MR\/V033867\/1"],"award-info":[{"award-number":["MR\/V033867\/1"]}]},{"name":"BHF","award":["AA\/18\/6\/34223"],"award-info":[{"award-number":["AA\/18\/6\/34223"]}]},{"name":"BHF","award":["PG\/18\/5033837"],"award-info":[{"award-number":["PG\/18\/5033837"]}]},{"name":"BHF","award":["PG\/22\/10989"],"award-info":[{"award-number":["PG\/22\/10989"]}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:p>\n                    The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted\n                    <jats:italic>cis<\/jats:italic>\n                    -Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11,\n                    <jats:italic>p<\/jats:italic>\n                    = 1.8 \u00d7 10\n                    <jats:sup>\u22123<\/jats:sup>\n                    ), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59,\n                    <jats:italic>p<\/jats:italic>\n                    = 1.5 \u00d7 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    ) and plasma tau concentration (0.06 log\n                    <jats:sub>2<\/jats:sub>\n                    (ng l\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) 95%CI 0.03; 0.08,\n                    <jats:italic>p<\/jats:italic>\n                    = 4.55 \u00d7 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    ). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.\n                  <\/jats:p>","DOI":"10.1098\/rsob.230419","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T19:05:39Z","timestamp":1721156739000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic evidence for serum amyloid P\u00a0component as a drug target in neurodegenerative disorders"],"prefix":"10.1098","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1327-0424","authenticated-orcid":true,"given":"A. Floriaan","family":"Schmidt","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Science, Faculty of Population Health, University College London, 69-75\u00a0Chenies\u00a0Mews, London WC1E 6HX, UK"},{"name":"UCL British Heart Foundation Research Accelerator, 69-75 Chenies Mews, London WC1E 6HX, UK"},{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam UMC, locatie AMC Postbus 22660, 1100 DD Amsterdam, Zuidoost, The\u00a0Netherlands"},{"name":"Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Finan","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, Faculty of Population Health, University College London, 69-75\u00a0Chenies\u00a0Mews, London WC1E 6HX, UK"},{"name":"UCL British Heart Foundation Research Accelerator, 69-75 Chenies Mews, London WC1E 6HX, UK"},{"name":"Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandesh","family":"Chopade","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, Faculty of Population Health, University College London, 69-75\u00a0Chenies\u00a0Mews, London WC1E 6HX, UK"},{"name":"UCL British Heart Foundation Research Accelerator, 69-75 Chenies Mews, London WC1E 6HX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Ellmerich","sequence":"additional","affiliation":[{"name":"Wolfson Drug Discovery Unit, Division of Medicine, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin N.","family":"Rossor","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, Queen Square, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-0081","authenticated-orcid":true,"given":"Aroon D.","family":"Hingorani","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, Faculty of Population Health, University College London, 69-75\u00a0Chenies\u00a0Mews, London WC1E 6HX, UK"},{"name":"UCL British Heart Foundation Research Accelerator, 69-75 Chenies Mews, London WC1E 6HX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2614-3248","authenticated-orcid":true,"given":"Mark\u00a0B.","family":"Pepys","sequence":"additional","affiliation":[{"name":"Wolfson Drug Discovery Unit, Division of Medicine, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(91)90090-Y"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1760"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902640106"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1556\/EuJMI.3.2013.4.8"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/13506129709003838"},{"key":"e_1_3_8_7_2","first-page":"284","article-title":"Binding of serum amyloid P-component (SAP) by amyloid fibrils","volume":"38","author":"Pepys MB","year":"1979","unstructured":"Pepys MB, Dyck RF, de Beer FC, Skinner M, Cohen AS. 1979 Binding of serum amyloid P-component (SAP) by amyloid fibrils. Clin. Exp. Immunol. 38, 284-293.","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4299"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1819"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-120076"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0897-855"},{"key":"e_1_3_8_12_2","unstructured":"Eli Lilly and Company.\u00a02023 Lilly's Donanemab significantly slowed cognitive and functional decline in phase 3 study of early Alzheimer's disease. See https:\/\/investor.lilly.com\/news-releases\/news-release-details\/lillys-donanemab-significantly-slowed-cognitive-and-functional\u00a0(accessed 26 May 2023)."},{"key":"e_1_3_8_13_2","unstructured":"Couzin-Frankel J. 2023 FDA approves new antibody to slow Alzheimer's disease even as safety concerns linger. Science \u00a0AAAS. 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Clin.\u00a0Exp. Immunol. 32, 119-124.","journal-title":"Clin.\u00a0Exp. Immunol."},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954-6820.1982.tb01959.x"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1159\/000017035"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0175-2"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00978-w"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27850-z"},{"key":"e_1_3_8_28_2","doi-asserted-by":"crossref","first-page":"a039230","DOI":"10.1101\/cshperspect.a039230","article-title":"Human genomics and drug development","volume":"12","author":"Schmidt AF","year":"2021","unstructured":"Schmidt AF, Hingorani AD, Finan C. 2021 Human genomics and drug development. Cold Spring Harb. Perspect. Med. 12, a039230. (doi:10.1101\/cshperspect.a039230)","journal-title":"Cold Spring Harb. Perspect. 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