Changes in iPSC-Astrocyte morphology reflect Alzheimer's disease patient clinical markers.

Autor:	Rowland HA; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Miller G; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Liu Q; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Oxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford OX3 7JX, UK.; School of Engineering Mathematics and Technology, University of Bristol, Bristol BS8 1TW, UK., Li S; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Sharp NR; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Ng B; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.; Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.; Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Republic of Singapore., Wei T; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Arunasalam K; Nuffield Department of Clinical Neurosciences, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Koychev I; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK., Hedegaard A; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK., Ribe EM; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Department of Old Age Psychiatry, Maurice Wohl Institute of Clinical Neurosciences, SE5 9RT, King's College London, London., Chan D; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.; Institute of Cognitive Neuroscience, University College London WC1N 3AR, UK., Chessell T; Neuroscience, Bio*P*harmaceuticals R&D, AstraZeneca, Granta Park, Cambridge, CB21 6GH, UK., Kocagoncu E; 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., Lawson J; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK., Malhotra P; Department of Brain Sciences, Imperial College London, Charing Cross Campus, London W6 8RP, UK., Ridha BH; Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK., Rowe JB; 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., Thomas AJ; Translational and Clinical Research Institute, Newcastle University, Newcastle, UK., Zamboni G; Nuffield Department of Clinical Neurosciences, Headington, University of Oxford, Oxford OX3 9DS, UK.; Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Ospedale Civile Baggiovara, 41126 Modena, Italy., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80 Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 6BG, UK.; UK Dementia Research Institute at UCL, London, WC1N 6BG, UK.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA., Cader MZ; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.; Nuffield Department of Clinical Neurosciences, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Wade-Martins R; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.; Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Lovestone S; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Currently at Janssen Medical UK, 50-100 Holmers Farm Way, High Wycombe HP12 4EG, UK., Nevado-Holgado A; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK., Kormilitzin A; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK., Buckley NJ; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Jazyk:	angličtina
Zdroj:	Stem cells (Dayton, Ohio) [Stem Cells] 2024 Dec 20. Date of Electronic Publication: 2024 Dec 20.
DOI:	10.1093/stmcls/sxae085
Abstrakt:	Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer's 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's disease (AD) reflect clinical markers, including β-amyloid (Aβ) 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 Aβ 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. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
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