Neurons derived from individual early Alzheimer's disease patients reflect their clinical vulnerability.

Autor:	Ng B; Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK., Rowland HA; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK., 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., Hayes EM; 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., Ribe EM; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK., Chan D; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK., Chessell T; Neuroscience, Innovative Medicines and Early Development, AstraZeneca AKB, Granta Park, Cambridge, CB21 6GH, UK., Ffytche D; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, SE5 8AF, UK., Gunn RN; Invicro & Department of Brain Sciences, Burlington Danes Building, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, 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 PA; 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., Buckley NJ; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK., Cader ZM; 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., Lovestone S; Department of Psychiatry, University of Oxford, Headington, Oxford OX3 7JX, UK.; Janssen Medical UK, 50-100 Holmers Farm Way, High Wycombe HP12 4EG, UK., Wade-Martins R; Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2022 Oct 21; Vol. 4 (6), pp. fcac267. Date of Electronic Publication: 2022 Oct 21 (Print Publication: 2022).
DOI:	10.1093/braincomms/fcac267
Abstrakt:	Establishing preclinical models of Alzheimer's 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's 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-β 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-β 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's disease pathology but also reflect key aspects of the clinical phenotypes of the same patients. Cellular models that reflect an individual's in-life clinical vulnerability thus represent a tractable method of Alzheimer's disease modelling using clinical data in combination with cellular phenotypes. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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