{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:45:32Z","timestamp":1791596732280,"version":"4.3.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council Dementias Platform UK Experimental Medicine Award","award":["MR\/M024962\/1"],"award-info":[{"award-number":["MR\/M024962\/1"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N029941\/1"],"award-info":[{"award-number":["MR\/N029941\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer\u2019s disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms. Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer\u2019s disease (AD) reflect clinical markers, including \u03b2-amyloid (A\u03b2) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets. In this work iPSC-derived astrocytes were generated from a cohort of individuals with high versus low levels of the inflammatory marker YKL-40, in their cerebrospinal fluid (CSF). iPSC-derived astrocytes were treated with exogenous A\u03b2 oligomers and high content imaging demonstrated a correlation between astrocytes that underwent the greatest morphology change from patients with low levels of CSF-YKL-40 and more protective APOE genotypes. This finding was subsequently verified using similarity learning as an unbiased approach. This study shows that iPSC-derived astrocytes from AD patients reflect key aspects of the pathophysiological phenotype of those same patients, thereby offering a novel means of modelling AD, stratifying AD patients and conducting therapeutic screens.<\/jats:p>","DOI":"10.1093\/stmcls\/sxae085","type":"journal-article","created":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T07:20:05Z","timestamp":1734160805000},"source":"Crossref","is-referenced-by-count":10,"title":["Changes in iPSC-astrocyte morphology reflect Alzheimer\u2019s disease patient clinical markers"],"prefix":"10.1093","volume":"43","author":[{"given":"Helen A","family":"Rowland","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Oxford , Headington , Oxford OX3 7JX ,","place":["United Kingdom"]},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford , Oxford OX1 3QU ,","place":["United 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Institute of Clinical Neurosciences, King\u2019s College London , London SE5 8AB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0QQ ,","place":["United Kingdom"]},{"name":"Institute of Cognitive Neuroscience, University College, London WC1N 3AR ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharani","family":"Chessell","sequence":"additional","affiliation":[{"name":"Neuroscience, BioPharmaceuticals R&D, AstraZeneca, Granta Park , Cambridge CB21 6GH ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 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