The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Haoshen Shi - One of the best experts on this subject based on the ideXlab platform.
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APP_SWE/PS1_ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice ( P
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer's disease.
Acta neuropathologica communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P
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Alzheimer's Retinopathy: Seeing Disease in the Eyes.
Frontiers in neuroscience, 2020Co-Authors: Nazanin Mirzaei, Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Julia Sheyn, Dieu-trang Fuchs, Keith L. Black, Mia Oviatt, Jonah Doustar, Maya Koronyo-hamaouiAbstract:The neurosensory retina emerges as a prominent site of Alzheimer’s disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that could, at least in part, be attributed to retinal damage. Over a decade ago, our group identified the main pathological hallmark of AD, amyloid β-protein (Aβ) plaques, in the retina of patients including early-stage clinical cases. Subsequent histological, biochemical and in vivo retinal imaging studies in animal models and in humans corroborated these findings and further revealed other signs of AD neuropathology in the retina. Among these signs, hyperphosphorylated tau, neuronal degeneration, retinal thinning, Vascular abnormalities and gliosis were documented. Further, linear correlations between the severity of retinal and brain Aβ concentrations and plaque pathology were described. More recently, extensive retinal pericyte loss along with Vascular platelet-derived growth factor receptor-β deficiency were discovered in postmortem retinas of MCI and AD patients. This progressive loss was closely associated with increased retinal Vascular Amyloidosis and predicted cerebral amyloid angiopathy scores. The new developments brought excitement to the field of retinal exploration in AD. Indeed, many questions still remain open, such as queries related to the temporal progression of AD-related pathology in the retina compared to the brain, the relations between retinal and cerebral changes and whether retinal signs can predict cognitive decline. The extent to which AD affects the retina, including the susceptibility of certain topographical regions and cell types, are further under intense investigation. Advances in retinal amyloid imaging, hyperspectral imaging, optical coherence tomography, and OCT-angiography encourage the use of such modalities to achieve more accurate, patient- and user-friendly, noninvasive detection and monitoring of AD. In this review, we summarize the current status in the field while addressing the many unknowns regarding Alzheimer’s retinopathy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer’s disease retina
Acta Neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony R. RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ_40 and Aβ_42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ_40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer's disease retina.
Acta neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ40 and Aβ42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer's retina implies compromised blood-retinal barrier integrity and provides new targets for AD diagnosis and therapy.
Maya Koronyo-hamaoui - One of the best experts on this subject based on the ideXlab platform.
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APP_SWE/PS1_ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice ( P
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer's disease.
Acta neuropathologica communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P
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Alzheimer's Retinopathy: Seeing Disease in the Eyes.
Frontiers in neuroscience, 2020Co-Authors: Nazanin Mirzaei, Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Julia Sheyn, Dieu-trang Fuchs, Keith L. Black, Mia Oviatt, Jonah Doustar, Maya Koronyo-hamaouiAbstract:The neurosensory retina emerges as a prominent site of Alzheimer’s disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that could, at least in part, be attributed to retinal damage. Over a decade ago, our group identified the main pathological hallmark of AD, amyloid β-protein (Aβ) plaques, in the retina of patients including early-stage clinical cases. Subsequent histological, biochemical and in vivo retinal imaging studies in animal models and in humans corroborated these findings and further revealed other signs of AD neuropathology in the retina. Among these signs, hyperphosphorylated tau, neuronal degeneration, retinal thinning, Vascular abnormalities and gliosis were documented. Further, linear correlations between the severity of retinal and brain Aβ concentrations and plaque pathology were described. More recently, extensive retinal pericyte loss along with Vascular platelet-derived growth factor receptor-β deficiency were discovered in postmortem retinas of MCI and AD patients. This progressive loss was closely associated with increased retinal Vascular Amyloidosis and predicted cerebral amyloid angiopathy scores. The new developments brought excitement to the field of retinal exploration in AD. Indeed, many questions still remain open, such as queries related to the temporal progression of AD-related pathology in the retina compared to the brain, the relations between retinal and cerebral changes and whether retinal signs can predict cognitive decline. The extent to which AD affects the retina, including the susceptibility of certain topographical regions and cell types, are further under intense investigation. Advances in retinal amyloid imaging, hyperspectral imaging, optical coherence tomography, and OCT-angiography encourage the use of such modalities to achieve more accurate, patient- and user-friendly, noninvasive detection and monitoring of AD. In this review, we summarize the current status in the field while addressing the many unknowns regarding Alzheimer’s retinopathy.
Yosef Koronyo - One of the best experts on this subject based on the ideXlab platform.
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APP_SWE/PS1_ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice ( P
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer's disease.
Acta neuropathologica communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P
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Alzheimer's Retinopathy: Seeing Disease in the Eyes.
Frontiers in neuroscience, 2020Co-Authors: Nazanin Mirzaei, Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Julia Sheyn, Dieu-trang Fuchs, Keith L. Black, Mia Oviatt, Jonah Doustar, Maya Koronyo-hamaouiAbstract:The neurosensory retina emerges as a prominent site of Alzheimer’s disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that could, at least in part, be attributed to retinal damage. Over a decade ago, our group identified the main pathological hallmark of AD, amyloid β-protein (Aβ) plaques, in the retina of patients including early-stage clinical cases. Subsequent histological, biochemical and in vivo retinal imaging studies in animal models and in humans corroborated these findings and further revealed other signs of AD neuropathology in the retina. Among these signs, hyperphosphorylated tau, neuronal degeneration, retinal thinning, Vascular abnormalities and gliosis were documented. Further, linear correlations between the severity of retinal and brain Aβ concentrations and plaque pathology were described. More recently, extensive retinal pericyte loss along with Vascular platelet-derived growth factor receptor-β deficiency were discovered in postmortem retinas of MCI and AD patients. This progressive loss was closely associated with increased retinal Vascular Amyloidosis and predicted cerebral amyloid angiopathy scores. The new developments brought excitement to the field of retinal exploration in AD. Indeed, many questions still remain open, such as queries related to the temporal progression of AD-related pathology in the retina compared to the brain, the relations between retinal and cerebral changes and whether retinal signs can predict cognitive decline. The extent to which AD affects the retina, including the susceptibility of certain topographical regions and cell types, are further under intense investigation. Advances in retinal amyloid imaging, hyperspectral imaging, optical coherence tomography, and OCT-angiography encourage the use of such modalities to achieve more accurate, patient- and user-friendly, noninvasive detection and monitoring of AD. In this review, we summarize the current status in the field while addressing the many unknowns regarding Alzheimer’s retinopathy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer’s disease retina
Acta Neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony R. RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ_40 and Aβ_42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ_40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer's disease retina.
Acta neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ40 and Aβ42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer's retina implies compromised blood-retinal barrier integrity and provides new targets for AD diagnosis and therapy.
Julia Sheyn - One of the best experts on this subject based on the ideXlab platform.
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APP_SWE/PS1_ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice ( P
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer's disease.
Acta neuropathologica communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P
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Alzheimer's Retinopathy: Seeing Disease in the Eyes.
Frontiers in neuroscience, 2020Co-Authors: Nazanin Mirzaei, Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Julia Sheyn, Dieu-trang Fuchs, Keith L. Black, Mia Oviatt, Jonah Doustar, Maya Koronyo-hamaouiAbstract:The neurosensory retina emerges as a prominent site of Alzheimer’s disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that could, at least in part, be attributed to retinal damage. Over a decade ago, our group identified the main pathological hallmark of AD, amyloid β-protein (Aβ) plaques, in the retina of patients including early-stage clinical cases. Subsequent histological, biochemical and in vivo retinal imaging studies in animal models and in humans corroborated these findings and further revealed other signs of AD neuropathology in the retina. Among these signs, hyperphosphorylated tau, neuronal degeneration, retinal thinning, Vascular abnormalities and gliosis were documented. Further, linear correlations between the severity of retinal and brain Aβ concentrations and plaque pathology were described. More recently, extensive retinal pericyte loss along with Vascular platelet-derived growth factor receptor-β deficiency were discovered in postmortem retinas of MCI and AD patients. This progressive loss was closely associated with increased retinal Vascular Amyloidosis and predicted cerebral amyloid angiopathy scores. The new developments brought excitement to the field of retinal exploration in AD. Indeed, many questions still remain open, such as queries related to the temporal progression of AD-related pathology in the retina compared to the brain, the relations between retinal and cerebral changes and whether retinal signs can predict cognitive decline. The extent to which AD affects the retina, including the susceptibility of certain topographical regions and cell types, are further under intense investigation. Advances in retinal amyloid imaging, hyperspectral imaging, optical coherence tomography, and OCT-angiography encourage the use of such modalities to achieve more accurate, patient- and user-friendly, noninvasive detection and monitoring of AD. In this review, we summarize the current status in the field while addressing the many unknowns regarding Alzheimer’s retinopathy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer’s disease retina
Acta Neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony R. RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ_40 and Aβ_42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ_40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer's disease retina.
Acta neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ40 and Aβ42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer's retina implies compromised blood-retinal barrier integrity and provides new targets for AD diagnosis and therapy.
Dieu-trang Fuchs - One of the best experts on this subject based on the ideXlab platform.
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APP_SWE/PS1_ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice ( P
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Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer's disease.
Acta neuropathologica communications, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Julia Sheyn, Dieu-trang Fuchs, Kolja Wawrowsky, Shouri Lahiri, Keith L. Black, Maya Koronyo-hamaouiAbstract:Extensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are Vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with Vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal Vascular changes and their possible relationships with Vascular Amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, Vascular Amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal Vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P
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Alzheimer's Retinopathy: Seeing Disease in the Eyes.
Frontiers in neuroscience, 2020Co-Authors: Nazanin Mirzaei, Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Julia Sheyn, Dieu-trang Fuchs, Keith L. Black, Mia Oviatt, Jonah Doustar, Maya Koronyo-hamaouiAbstract:The neurosensory retina emerges as a prominent site of Alzheimer’s disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that could, at least in part, be attributed to retinal damage. Over a decade ago, our group identified the main pathological hallmark of AD, amyloid β-protein (Aβ) plaques, in the retina of patients including early-stage clinical cases. Subsequent histological, biochemical and in vivo retinal imaging studies in animal models and in humans corroborated these findings and further revealed other signs of AD neuropathology in the retina. Among these signs, hyperphosphorylated tau, neuronal degeneration, retinal thinning, Vascular abnormalities and gliosis were documented. Further, linear correlations between the severity of retinal and brain Aβ concentrations and plaque pathology were described. More recently, extensive retinal pericyte loss along with Vascular platelet-derived growth factor receptor-β deficiency were discovered in postmortem retinas of MCI and AD patients. This progressive loss was closely associated with increased retinal Vascular Amyloidosis and predicted cerebral amyloid angiopathy scores. The new developments brought excitement to the field of retinal exploration in AD. Indeed, many questions still remain open, such as queries related to the temporal progression of AD-related pathology in the retina compared to the brain, the relations between retinal and cerebral changes and whether retinal signs can predict cognitive decline. The extent to which AD affects the retina, including the susceptibility of certain topographical regions and cell types, are further under intense investigation. Advances in retinal amyloid imaging, hyperspectral imaging, optical coherence tomography, and OCT-angiography encourage the use of such modalities to achieve more accurate, patient- and user-friendly, noninvasive detection and monitoring of AD. In this review, we summarize the current status in the field while addressing the many unknowns regarding Alzheimer’s retinopathy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer’s disease retina
Acta Neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony R. RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ_40 and Aβ_42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ_40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.
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Identification of early pericyte loss and Vascular Amyloidosis in Alzheimer's disease retina.
Acta neuropathologica, 2020Co-Authors: Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony RodriguezAbstract:Pericyte loss and deficient Vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of Vascular-structural abnormalities and Vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal Vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-Vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in Vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal Vascular Aβ40 and Aβ42 burden. Decreased Vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal Vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased Vascular Amyloidosis in Alzheimer's retina implies compromised blood-retinal barrier integrity and provides new targets for AD diagnosis and therapy.
