{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:35:57Z","timestamp":1792100157482,"version":"4.4.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research-Medical Research Council Dementias Platform UK Experimental Medicine Award","award":["MR\/L023784\/2"],"award-info":[{"award-number":["MR\/L023784\/2"]}]},{"name":"Equipment Award","award":["MR\/M024962\/1"],"award-info":[{"award-number":["MR\/M024962\/1"]}]},{"name":"Medical Research Council","award":["MR\/N029941\/1"],"award-info":[{"award-number":["MR\/N029941\/1"]}]},{"name":"Stem Cells for Biological Assays of Novel Drugs and Predictive Toxicology"},{"name":"Innovative Medicines Initiative Joint Undertaking","award":["115439"],"award-info":[{"award-number":["115439"]}]},{"name":"European Union\u2019s Seventh Framework Programme","award":["FP7\/2007e2013"],"award-info":[{"award-number":["FP7\/2007e2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Establishing preclinical models of Alzheimer\u2019s disease that predict clinical outcomes remains a critically important, yet to date not fully realized, goal. Models derived from human cells offer considerable advantages over non-human models, including the potential to reflect some of the inter-individual differences that are apparent in patients. Here we report an approach using induced pluripotent stem cell-derived cortical neurons from people with early symptomatic Alzheimer\u2019s disease where we sought a match between individual disease characteristics in the cells with analogous characteristics in the people from whom they were derived. We show that the response to amyloid-\u03b2 burden in life, as measured by cognitive decline and brain activity levels, varies between individuals and this vulnerability rating correlates with the individual cellular vulnerability to extrinsic amyloid-\u03b2 in vitro as measured by synapse loss and function. Our findings indicate that patient-induced pluripotent stem cell-derived cortical neurons not only present key aspects of Alzheimer\u2019s disease pathology but also reflect key aspects of the clinical phenotypes of the same patients. Cellular models that reflect an individual\u2019s in-life clinical vulnerability thus represent a tractable method of Alzheimer\u2019s disease modelling using clinical data in combination with cellular phenotypes.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac267","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T13:30:04Z","timestamp":1666272604000},"source":"Crossref","is-referenced-by-count":19,"title":["Neurons derived from individual early Alzheimer\u2019s disease patients reflect their clinical vulnerability"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6819-0176","authenticated-orcid":false,"given":"Bryan","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Physiology Anatomy and Genetics, University of Oxford , South Parks Road, Oxford OX1 3QU , UK"},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen A","family":"Rowland","sequence":"additional","affiliation":[{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"},{"name":"Department of Psychiatry, University of Oxford, Headington , Oxford OX3 7JX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Wei","sequence":"additional","affiliation":[{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"},{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanisa","family":"Arunasalam","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma Mee","family":"Hayes","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Koychev","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Headington , Oxford OX3 7JX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hedegaard","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Headington , Oxford OX3 7JX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena M","family":"Ribe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Headington , Oxford OX3 7JX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharani","family":"Chessell","sequence":"additional","affiliation":[{"name":"Neuroscience, Innovative Medicines and Early Development, AstraZeneca AKB, Granta Park , Cambridge, CB21 6GH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Ffytche","sequence":"additional","affiliation":[{"name":"Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, Kings College London , London, SE5 8AF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger N","family":"Gunn","sequence":"additional","affiliation":[{"name":"Invicro & Department of Brain Sciences, Burlington Danes Building, Imperial College London, Hammersmith Hospital , Du Cane Road, London, W12 0NN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-7472","authenticated-orcid":false,"given":"Ece","family":"Kocagoncu","sequence":"additional","affiliation":[{"name":"Medical Research Council Cognition and Brain Sciences Unit, Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 7EF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lawson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Headington , Oxford OX3 7JX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-0780","authenticated-orcid":false,"given":"Paresh A","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London , Charing Cross Campus, London W6 8RP , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-9922","authenticated-orcid":false,"given":"Basil H","family":"Ridha","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Institute of Neurology, Queen Square , London, WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B","family":"Rowe","sequence":"additional","affiliation":[{"name":"Medical Research Council Cognition and Brain Sciences Unit, Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 7EF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J","family":"Thomas","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6133-3373","authenticated-orcid":false,"given":"Giovanna","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, Headington, University of Oxford , Oxford OX3 9DS , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel J","family":"Buckley","sequence":"additional","affiliation":[{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"},{"name":"Department of Psychiatry, University of Oxford, Headington , Oxford OX3 7JX , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-406X","authenticated-orcid":false,"given":"Zameel M","family":"Cader","sequence":"additional","affiliation":[{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"},{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lovestone","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Headington , Oxford OX3 7JX , UK"},{"name":"Janssen Medical UK, 50-100 Holmers Farm Way , High Wycombe HP12 4EG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Wade-Martins","sequence":"additional","affiliation":[{"name":"Department of Physiology Anatomy and Genetics, University of Oxford , South Parks Road, Oxford OX1 3QU , UK"},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford , Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU , 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