Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy

Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other typ...
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Autor*in:	Yingjian You [verfasserIn] Abigail Perkins [verfasserIn] Pablo Cisternas [verfasserIn] Braulio Muñoz [verfasserIn] Xavier Taylor [verfasserIn] Yanwen You [verfasserIn] Holly J. Garringer [verfasserIn] Adrian L. Oblak [verfasserIn] Brady K. Atwood [verfasserIn] Ruben Vidal [verfasserIn] Cristian A. Lasagna-Reeves [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration

Übergeordnetes Werk:	In: Acta Neuropathologica Communications - BMC, 2013, 7(2019), 1, Seite 15
Übergeordnetes Werk:	volume:7 ; year:2019 ; number:1 ; pages:15

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s40478-019-0680-z

Katalog-ID:	DOAJ066520894

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520			\|a Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA.
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allfields	10.1186/s40478-019-0680-z doi (DE-627)DOAJ066520894 (DE-599)DOAJf13f3d57db374806ad1c437a7454c5eb DE-627 ger DE-627 rakwb eng RC346-429 Yingjian You verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA. Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration Neurology. Diseases of the nervous system Abigail Perkins verfasserin aut Pablo Cisternas verfasserin aut Braulio Muñoz verfasserin aut Xavier Taylor verfasserin aut Yanwen You verfasserin aut Holly J. Garringer verfasserin aut Adrian L. Oblak verfasserin aut Brady K. Atwood verfasserin aut Ruben Vidal verfasserin aut Cristian A. Lasagna-Reeves verfasserin aut In Acta Neuropathologica Communications BMC, 2013 7(2019), 1, Seite 15 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/article/f13f3d57db374806ad1c437a7454c5eb kostenfrei http://link.springer.com/article/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15
spelling	10.1186/s40478-019-0680-z doi (DE-627)DOAJ066520894 (DE-599)DOAJf13f3d57db374806ad1c437a7454c5eb DE-627 ger DE-627 rakwb eng RC346-429 Yingjian You verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA. Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration Neurology. Diseases of the nervous system Abigail Perkins verfasserin aut Pablo Cisternas verfasserin aut Braulio Muñoz verfasserin aut Xavier Taylor verfasserin aut Yanwen You verfasserin aut Holly J. Garringer verfasserin aut Adrian L. Oblak verfasserin aut Brady K. Atwood verfasserin aut Ruben Vidal verfasserin aut Cristian A. Lasagna-Reeves verfasserin aut In Acta Neuropathologica Communications BMC, 2013 7(2019), 1, Seite 15 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/article/f13f3d57db374806ad1c437a7454c5eb kostenfrei http://link.springer.com/article/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15
allfields_unstemmed	10.1186/s40478-019-0680-z doi (DE-627)DOAJ066520894 (DE-599)DOAJf13f3d57db374806ad1c437a7454c5eb DE-627 ger DE-627 rakwb eng RC346-429 Yingjian You verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA. Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration Neurology. Diseases of the nervous system Abigail Perkins verfasserin aut Pablo Cisternas verfasserin aut Braulio Muñoz verfasserin aut Xavier Taylor verfasserin aut Yanwen You verfasserin aut Holly J. Garringer verfasserin aut Adrian L. Oblak verfasserin aut Brady K. Atwood verfasserin aut Ruben Vidal verfasserin aut Cristian A. Lasagna-Reeves verfasserin aut In Acta Neuropathologica Communications BMC, 2013 7(2019), 1, Seite 15 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/article/f13f3d57db374806ad1c437a7454c5eb kostenfrei http://link.springer.com/article/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15
allfieldsGer	10.1186/s40478-019-0680-z doi (DE-627)DOAJ066520894 (DE-599)DOAJf13f3d57db374806ad1c437a7454c5eb DE-627 ger DE-627 rakwb eng RC346-429 Yingjian You verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA. Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration Neurology. Diseases of the nervous system Abigail Perkins verfasserin aut Pablo Cisternas verfasserin aut Braulio Muñoz verfasserin aut Xavier Taylor verfasserin aut Yanwen You verfasserin aut Holly J. Garringer verfasserin aut Adrian L. Oblak verfasserin aut Brady K. Atwood verfasserin aut Ruben Vidal verfasserin aut Cristian A. Lasagna-Reeves verfasserin aut In Acta Neuropathologica Communications BMC, 2013 7(2019), 1, Seite 15 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/article/f13f3d57db374806ad1c437a7454c5eb kostenfrei http://link.springer.com/article/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15
allfieldsSound	10.1186/s40478-019-0680-z doi (DE-627)DOAJ066520894 (DE-599)DOAJf13f3d57db374806ad1c437a7454c5eb DE-627 ger DE-627 rakwb eng RC346-429 Yingjian You verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA. Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration Neurology. Diseases of the nervous system Abigail Perkins verfasserin aut Pablo Cisternas verfasserin aut Braulio Muñoz verfasserin aut Xavier Taylor verfasserin aut Yanwen You verfasserin aut Holly J. Garringer verfasserin aut Adrian L. Oblak verfasserin aut Brady K. Atwood verfasserin aut Ruben Vidal verfasserin aut Cristian A. Lasagna-Reeves verfasserin aut In Acta Neuropathologica Communications BMC, 2013 7(2019), 1, Seite 15 (DE-627)746066465 (DE-600)2715589-4 20515960 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/article/f13f3d57db374806ad1c437a7454c5eb kostenfrei http://link.springer.com/article/10.1186/s40478-019-0680-z kostenfrei https://doaj.org/toc/2051-5960 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15
language	English
source	In Acta Neuropathologica Communications 7(2019), 1, Seite 15 volume:7 year:2019 number:1 pages:15
sourceStr	In Acta Neuropathologica Communications 7(2019), 1, Seite 15 volume:7 year:2019 number:1 pages:15
format_phy_str_mv	Article
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topic_facet	Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration Neurology. Diseases of the nervous system
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spellingShingle	Yingjian You misc RC346-429 misc Cerebral amyloid angiopathy misc Tau oligomers misc ADan oligomers misc Vascular amyloid misc Tau downregulation misc Neurodegeneration misc Neurology. Diseases of the nervous system Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
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topic_title	RC346-429 Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration
topic	misc RC346-429 misc Cerebral amyloid angiopathy misc Tau oligomers misc ADan oligomers misc Vascular amyloid misc Tau downregulation misc Neurodegeneration misc Neurology. Diseases of the nervous system
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title	Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
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title_full	Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
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title_sort	tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
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title_auth	Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
abstract	Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA.
abstractGer	Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA.
abstract_unstemmed	Abstract Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA.
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Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature. Interestingly, in many cases, vascular amyloidosis is accompanied by significant tau pathology. However, the contribution of tau to neurodegeneration associated to CAA remains to be determined. We used a mouse model of Familial Danish Dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature, to characterize the contribution of tau to neurodegeneration associated to CAA. We performed histological and biochemical assays to establish tau modifications associated with CAA in conjunction with cell-based and electrophysiological assays to determine the role of tau in the synaptic dysfunction associated with ADan. We demonstrated that ADan aggregates induced hyperphosphorylation and misfolding of tau. Moreover, in a mouse model for CAA, we observed tau oligomers closely associated to astrocytes in the vicinity of vascular amyloid deposits. We finally determined that the absence of tau prevents synaptic dysfunction induced by ADan oligomers. In addition to demonstrating the effect of ADan amyloid on tau misfolding, our results provide compelling evidence of the role of tau in neurodegeneration associated with ADan-CAA and suggest that decreasing tau levels could be a feasible approach for the treatment of CAA.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cerebral amyloid angiopathy</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tau oligomers</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ADan oligomers</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Vascular amyloid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tau downregulation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Neurodegeneration</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neurology. Diseases of the nervous system</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Abigail Perkins</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pablo Cisternas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Braulio Muñoz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xavier Taylor</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yanwen You</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Holly J. 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Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy

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