Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology
Alzheimer’s disease (AD), characterized by memory loss and cognitive decline, affects nearly 50 million people worldwide. Amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of phosphorylated Tau protein (pTau) are key histopathological features of the disease in the brain, an...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2024.1340448/full |
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| author | Ethan James Anne Vielle Anne Vielle Karen Cusato Helen Li Byoungin Lee Shama Parween Anna Howell Noah R. Johnson Noah R. Johnson Noah R. Johnson Heidi J. Chial Heidi J. Chial Heidi J. Chial Huntington Potter Huntington Potter Huntington Potter M. Natalia Vergara M. Natalia Vergara M. Natalia Vergara |
| author_facet | Ethan James Anne Vielle Anne Vielle Karen Cusato Helen Li Byoungin Lee Shama Parween Anna Howell Noah R. Johnson Noah R. Johnson Noah R. Johnson Heidi J. Chial Heidi J. Chial Heidi J. Chial Huntington Potter Huntington Potter Huntington Potter M. Natalia Vergara M. Natalia Vergara M. Natalia Vergara |
| author_sort | Ethan James |
| collection | DOAJ |
| description | Alzheimer’s disease (AD), characterized by memory loss and cognitive decline, affects nearly 50 million people worldwide. Amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of phosphorylated Tau protein (pTau) are key histopathological features of the disease in the brain, and recent advances have also identified AD histopathology in the retina. Thus, the retina represents a central nervous system (CNS) tissue highly amenable to non-invasive diagnostic imaging that shows promise as a biomarker for early AD. Given the devastating effects of AD on patients, their families, and society, new treatment modalities that can significantly alter the disease course are urgently needed. In this study, we have developed and characterized a novel human retinal organoid (RO) model derived from induced pluripotent stem cells (iPSCs) from patients with familial AD due to mutations in the amyloid precursor protein gene (APP). Using immunofluorescence and histological staining, we evaluated the cellular composition and AD histopathological features of AD-ROs compared to control ROs from healthy individuals. We found that AD-ROs largely resemble their healthy control counterparts in cellular composition but display increased levels of Aβ and pTau. We also present proof of principle of an assay to quantify amyloid levels in whole ROs. This in vitro model of the human AD retina constitutes a new tool for drug screening, biomarker discovery, and pathophysiological studies. |
| first_indexed | 2024-03-08T12:07:21Z |
| format | Article |
| id | doaj.art-0957290644124230b47f85a5b23448f7 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-08T12:07:21Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-0957290644124230b47f85a5b23448f72024-01-23T04:25:08ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022024-01-011810.3389/fncel.2024.13404481340448Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathologyEthan James0Anne Vielle1Anne Vielle2Karen Cusato3Helen Li4Byoungin Lee5Shama Parween6Anna Howell7Noah R. Johnson8Noah R. Johnson9Noah R. Johnson10Heidi J. Chial11Heidi J. Chial12Heidi J. Chial13Huntington Potter14Huntington Potter15Huntington Potter16M. Natalia Vergara17M. Natalia Vergara18M. Natalia Vergara19CellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesCellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesCellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesCellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesCellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesCellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesCellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesUniversity of Colorado Alzheimer’s and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesUniversity of Colorado Alzheimer’s and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesUniversity of Colorado Alzheimer’s and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesCellSight Ocular Stem Cell and Regeneration Research Program, Sue Anschutz-Rodgers Eye Center, University of Colorado School of Medicine, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesUniversity of Colorado Alzheimer’s and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesAlzheimer’s disease (AD), characterized by memory loss and cognitive decline, affects nearly 50 million people worldwide. Amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of phosphorylated Tau protein (pTau) are key histopathological features of the disease in the brain, and recent advances have also identified AD histopathology in the retina. Thus, the retina represents a central nervous system (CNS) tissue highly amenable to non-invasive diagnostic imaging that shows promise as a biomarker for early AD. Given the devastating effects of AD on patients, their families, and society, new treatment modalities that can significantly alter the disease course are urgently needed. In this study, we have developed and characterized a novel human retinal organoid (RO) model derived from induced pluripotent stem cells (iPSCs) from patients with familial AD due to mutations in the amyloid precursor protein gene (APP). Using immunofluorescence and histological staining, we evaluated the cellular composition and AD histopathological features of AD-ROs compared to control ROs from healthy individuals. We found that AD-ROs largely resemble their healthy control counterparts in cellular composition but display increased levels of Aβ and pTau. We also present proof of principle of an assay to quantify amyloid levels in whole ROs. This in vitro model of the human AD retina constitutes a new tool for drug screening, biomarker discovery, and pathophysiological studies.https://www.frontiersin.org/articles/10.3389/fncel.2024.1340448/fullhiPSCretinaorganoidAlzheimer’s diseasedisease modeling |
| spellingShingle | Ethan James Anne Vielle Anne Vielle Karen Cusato Helen Li Byoungin Lee Shama Parween Anna Howell Noah R. Johnson Noah R. Johnson Noah R. Johnson Heidi J. Chial Heidi J. Chial Heidi J. Chial Huntington Potter Huntington Potter Huntington Potter M. Natalia Vergara M. Natalia Vergara M. Natalia Vergara Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology Frontiers in Cellular Neuroscience hiPSC retina organoid Alzheimer’s disease disease modeling |
| title | Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology |
| title_full | Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology |
| title_fullStr | Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology |
| title_full_unstemmed | Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology |
| title_short | Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology |
| title_sort | human ipsc derived retinal organoids develop robust alzheimer s disease neuropathology |
| topic | hiPSC retina organoid Alzheimer’s disease disease modeling |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2024.1340448/full |
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