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:	You, Yingjian [verfasserIn] Perkins, Abigail Cisternas, Pablo Muñoz, Braulio Taylor, Xavier You, Yanwen Garringer, Holly J. Oblak, Adrian L. Atwood, Brady K. Vidal, Ruben Lasagna-Reeves, Cristian A.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

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

Anmerkung:	© The Author(s). 2019

Übergeordnetes Werk:	Enthalten in: Acta Neuropathologica Communications - London : Biomed Central, 2013, 7(2019), 1 vom: 26. Feb.
Übergeordnetes Werk:	volume:7 ; year:2019 ; number:1 ; day:26 ; month:02

Links:	Volltext

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

Katalog-ID:	SPR036514764

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allfields	10.1186/s40478-019-0680-z doi (DE-627)SPR036514764 (SPR)s40478-019-0680-z-e DE-627 ger DE-627 rakwb eng You, Yingjian verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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 (dpeaa)DE-He213 Tau oligomers (dpeaa)DE-He213 ADan oligomers (dpeaa)DE-He213 Vascular amyloid (dpeaa)DE-He213 Tau downregulation (dpeaa)DE-He213 Neurodegeneration (dpeaa)DE-He213 Perkins, Abigail aut Cisternas, Pablo aut Muñoz, Braulio aut Taylor, Xavier aut You, Yanwen aut Garringer, Holly J. aut Oblak, Adrian L. aut Atwood, Brady K. aut Vidal, Ruben aut Lasagna-Reeves, Cristian A. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 7(2019), 1 vom: 26. Feb. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:7 year:2019 number:1 day:26 month:02 https://dx.doi.org/10.1186/s40478-019-0680-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 26 02
spelling	10.1186/s40478-019-0680-z doi (DE-627)SPR036514764 (SPR)s40478-019-0680-z-e DE-627 ger DE-627 rakwb eng You, Yingjian verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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 (dpeaa)DE-He213 Tau oligomers (dpeaa)DE-He213 ADan oligomers (dpeaa)DE-He213 Vascular amyloid (dpeaa)DE-He213 Tau downregulation (dpeaa)DE-He213 Neurodegeneration (dpeaa)DE-He213 Perkins, Abigail aut Cisternas, Pablo aut Muñoz, Braulio aut Taylor, Xavier aut You, Yanwen aut Garringer, Holly J. aut Oblak, Adrian L. aut Atwood, Brady K. aut Vidal, Ruben aut Lasagna-Reeves, Cristian A. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 7(2019), 1 vom: 26. Feb. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:7 year:2019 number:1 day:26 month:02 https://dx.doi.org/10.1186/s40478-019-0680-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 26 02
allfields_unstemmed	10.1186/s40478-019-0680-z doi (DE-627)SPR036514764 (SPR)s40478-019-0680-z-e DE-627 ger DE-627 rakwb eng You, Yingjian verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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 (dpeaa)DE-He213 Tau oligomers (dpeaa)DE-He213 ADan oligomers (dpeaa)DE-He213 Vascular amyloid (dpeaa)DE-He213 Tau downregulation (dpeaa)DE-He213 Neurodegeneration (dpeaa)DE-He213 Perkins, Abigail aut Cisternas, Pablo aut Muñoz, Braulio aut Taylor, Xavier aut You, Yanwen aut Garringer, Holly J. aut Oblak, Adrian L. aut Atwood, Brady K. aut Vidal, Ruben aut Lasagna-Reeves, Cristian A. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 7(2019), 1 vom: 26. Feb. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:7 year:2019 number:1 day:26 month:02 https://dx.doi.org/10.1186/s40478-019-0680-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 26 02
allfieldsGer	10.1186/s40478-019-0680-z doi (DE-627)SPR036514764 (SPR)s40478-019-0680-z-e DE-627 ger DE-627 rakwb eng You, Yingjian verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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 (dpeaa)DE-He213 Tau oligomers (dpeaa)DE-He213 ADan oligomers (dpeaa)DE-He213 Vascular amyloid (dpeaa)DE-He213 Tau downregulation (dpeaa)DE-He213 Neurodegeneration (dpeaa)DE-He213 Perkins, Abigail aut Cisternas, Pablo aut Muñoz, Braulio aut Taylor, Xavier aut You, Yanwen aut Garringer, Holly J. aut Oblak, Adrian L. aut Atwood, Brady K. aut Vidal, Ruben aut Lasagna-Reeves, Cristian A. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 7(2019), 1 vom: 26. Feb. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:7 year:2019 number:1 day:26 month:02 https://dx.doi.org/10.1186/s40478-019-0680-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 26 02
allfieldsSound	10.1186/s40478-019-0680-z doi (DE-627)SPR036514764 (SPR)s40478-019-0680-z-e DE-627 ger DE-627 rakwb eng You, Yingjian verfasserin aut Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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 (dpeaa)DE-He213 Tau oligomers (dpeaa)DE-He213 ADan oligomers (dpeaa)DE-He213 Vascular amyloid (dpeaa)DE-He213 Tau downregulation (dpeaa)DE-He213 Neurodegeneration (dpeaa)DE-He213 Perkins, Abigail aut Cisternas, Pablo aut Muñoz, Braulio aut Taylor, Xavier aut You, Yanwen aut Garringer, Holly J. aut Oblak, Adrian L. aut Atwood, Brady K. aut Vidal, Ruben aut Lasagna-Reeves, Cristian A. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 7(2019), 1 vom: 26. Feb. (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:7 year:2019 number:1 day:26 month:02 https://dx.doi.org/10.1186/s40478-019-0680-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 26 02
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topic_facet	Cerebral amyloid angiopathy Tau oligomers ADan oligomers Vascular amyloid Tau downregulation Neurodegeneration
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author	You, Yingjian
spellingShingle	You, Yingjian misc Cerebral amyloid angiopathy misc Tau oligomers misc ADan oligomers misc Vascular amyloid misc Tau downregulation misc Neurodegeneration Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
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topic_title	Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy Cerebral amyloid angiopathy (dpeaa)DE-He213 Tau oligomers (dpeaa)DE-He213 ADan oligomers (dpeaa)DE-He213 Vascular amyloid (dpeaa)DE-He213 Tau downregulation (dpeaa)DE-He213 Neurodegeneration (dpeaa)DE-He213
topic	misc Cerebral amyloid angiopathy misc Tau oligomers misc ADan oligomers misc Vascular amyloid misc Tau downregulation misc Neurodegeneration
topic_unstemmed	misc Cerebral amyloid angiopathy misc Tau oligomers misc ADan oligomers misc Vascular amyloid misc Tau downregulation misc Neurodegeneration
topic_browse	misc Cerebral amyloid angiopathy misc Tau oligomers misc ADan oligomers misc Vascular amyloid misc Tau downregulation misc Neurodegeneration
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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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author_browse	You, Yingjian Perkins, Abigail Cisternas, Pablo Muñoz, Braulio Taylor, Xavier You, Yanwen Garringer, Holly J. Oblak, Adrian L. Atwood, Brady K. Vidal, Ruben Lasagna-Reeves, Cristian A.
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title_sort	tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
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. © The Author(s). 2019
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. © The Author(s). 2019
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. © The Author(s). 2019
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title_short	Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
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author2	Perkins, Abigail Cisternas, Pablo Muñoz, Braulio Taylor, Xavier You, Yanwen Garringer, Holly J. Oblak, Adrian L. Atwood, Brady K. Vidal, Ruben Lasagna-Reeves, Cristian A.
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up_date	2024-07-03T18:05:41.140Z
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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. 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Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy

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