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Your search keyword '"iPSC-microglia"' showing total 3 results
Start Over Descriptor "iPSC-microglia" Topic cerebral amyloid angiopathy
3 results on '"iPSC-microglia"'

1. Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice.

Author

Kiani Shabestari S, Morabito S, Danhash EP, McQuade A, Sanchez JR, Miyoshi E, Chadarevian JP, Claes C, Coburn MA, Hasselmann J, Hidalgo J, Tran KN, Martini AC, Chang Rothermich W, Pascual J, Head E, Hume DA, Pridans C, Davtyan H, Swarup V, and Blurton-Jones M

Subjects
Amyloid beta-Peptides metabolism, Animals, Brain metabolism, Disease Models, Animal, Humans, Induced Pluripotent Stem Cells, Membrane Glycoproteins, Mice, Mice, Transgenic, Plaque, Amyloid pathology, Receptors, Immunologic, Alzheimer Disease pathology, Cerebral Amyloid Angiopathy complications, Cerebral Amyloid Angiopathy pathology, Microglia metabolism
Abstract

Microglia are strongly implicated in the development and progression of Alzheimer's disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2., Competing Interests: Declaration of interests M.B.-J. is a co-inventor of patent application WO/2018/160496, related to the differentiation of pluripotent stem cells into microglia, and co-founder of NovoGlia. All other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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2. Absence of microglia promotes diverse pathologies and early lethality in Alzheimer’s disease mice

Author

Shabestari, Sepideh Kiani, Morabito, Samuel, Danhash, Emma Pascal, McQuade, Amanda, Sanchez, Jessica Ramirez, Miyoshi, Emily, Chadarevian, Jean Paul, Claes, Christel, Coburn, Morgan Alexandra, Hasselmann, Jonathan, Hidalgo, Jorge, Tran, Kayla Nhi, Martini, Alessandra C, Rothermich, Winston Chang, Pascual, Jesse, Head, Elizabeth, Hume, David A, Pridans, Clare, Davtyan, Hayk, Swarup, Vivek, and Blurton-Jones, Mathew

Subjects
Biochemistry and Cell Biology, Biological Sciences, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Alzheimer's Disease, Neurosciences, Genetics, Vascular Cognitive Impairment/Dementia, Neurodegenerative, Aging, Cerebrovascular, Dementia, Alzheimer's Disease Related Dementias (ADRD), Prevention, 2.1 Biological and endogenous factors, Neurological, Alzheimer Disease, Amyloid beta-Peptides, Animals, Brain, Cerebral Amyloid Angiopathy, Disease Models, Animal, Humans, Induced Pluripotent Stem Cells, Membrane Glycoproteins, Mice, Mice, Transgenic, Microglia, Plaque, Amyloid, Receptors, Immunologic, Alzheimer’s disease, Alzheimer’s disease co-pathologies, CP: Neuroscience, TREM2, brain calcification, cerebral amyloid angiopathy, hemorrhage, iPSC-microglia, microglia, mortality, neurovascular, Medical Physiology, Biological sciences
Abstract

Microglia are strongly implicated in the development and progression of Alzheimer's disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2.

Published
2022

3. Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice

Author

Sepideh Kiani Shabestari, Samuel Morabito, Emma Pascal Danhash, Amanda McQuade, Jessica Ramirez Sanchez, Emily Miyoshi, Jean Paul Chadarevian, Christel Claes, Morgan Alexandra Coburn, Jonathan Hasselmann, Jorge Hidalgo, Kayla Nhi Tran, Alessandra C. Martini, Winston Chang Rothermich, Jesse Pascual, Elizabeth Head, David A. Hume, Clare Pridans, Hayk Davtyan, Vivek Swarup, and Mathew Blurton-Jones

Subjects
Amyloid, Aging, brain calcification, neurovascular, Medical Physiology, Induced Pluripotent Stem Cells, microglia, Mice, Transgenic, Plaque, Amyloid, Neurodegenerative, Alzheimer's Disease, General Biochemistry, Genetics and Molecular Biology, Transgenic, Mice, Immunologic, Alzheimer Disease, Receptors, TREM2, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Animals, Humans, Alzheimer’s disease co-pathologies, Aetiology, Receptors, Immunologic, cerebral amyloid angiopathy, Plaque, iPSC-microglia, Amyloid beta-Peptides, Membrane Glycoproteins, Animal, Neuroscience [CP], Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain, mortality, Brain Disorders, Cerebral Amyloid Angiopathy, Disease Models, Animal, Disease Models, Neurological, Dementia, Biochemistry and Cell Biology, Microglia, hemorrhage, Alzheimer’s disease
Abstract

Microglia are strongly implicated in the development and progression of Alzheimer’s disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2.

Published
2021
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