Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity
While the spread of some neurodegenerative disease-associated proteinopathies, such as tau and α-synuclein, is well studied and clearly implicates transsynaptic pathology transmission, research into the progressive spread of amyloid-β pathology has been less clear. In fact, prior analyses of transre...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00653/full |
| _version_ | 1819293533290364928 |
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| author | Chris Mezias Ashish Raj Ashish Raj |
| author_facet | Chris Mezias Ashish Raj Ashish Raj |
| author_sort | Chris Mezias |
| collection | DOAJ |
| description | While the spread of some neurodegenerative disease-associated proteinopathies, such as tau and α-synuclein, is well studied and clearly implicates transsynaptic pathology transmission, research into the progressive spread of amyloid-β pathology has been less clear. In fact, prior analyses of transregional amyloid-β pathology spread have implicated both transsynaptic and other intracellular- as well as extracellular-based transmission mechanisms. We therefore conducted the current meta-analytic analysis to help assess whether spatiotemporal amyloid-β pathology development patterns in mouse models, where regional proteinopathy is more directly characterizable than in patients, better fit with transsynaptic- or extracellular-based theories of pathology spread. We find that, consistently across the datasets used in this study, spatiotemporal amyloid-β pathology patterns are more consistent with extracellular-based explanations of pathology spread. Furthermore, we find that regional levels of amyloid precursor protein in a mouse model are also better correlated with expected pathology patterns based on extracellular, rather than intracellular or transsynaptic spread. |
| first_indexed | 2024-12-24T04:11:56Z |
| format | Article |
| id | doaj.art-29d95acc60754d4497003eeabaa4d976 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-24T04:11:56Z |
| publishDate | 2017-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-29d95acc60754d4497003eeabaa4d9762022-12-21T17:16:03ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-12-01810.3389/fneur.2017.00653303527Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not ConnectivityChris Mezias0Ashish Raj1Ashish Raj2Department of Neuroscience, Weill Cornell Medicine of Cornell University, New York, NY, United StatesDepartment of Neuroscience, Weill Cornell Medicine of Cornell University, New York, NY, United StatesDepartment of Radiology, Weill Cornell Medicine of Cornell University, New York, NY, United StatesWhile the spread of some neurodegenerative disease-associated proteinopathies, such as tau and α-synuclein, is well studied and clearly implicates transsynaptic pathology transmission, research into the progressive spread of amyloid-β pathology has been less clear. In fact, prior analyses of transregional amyloid-β pathology spread have implicated both transsynaptic and other intracellular- as well as extracellular-based transmission mechanisms. We therefore conducted the current meta-analytic analysis to help assess whether spatiotemporal amyloid-β pathology development patterns in mouse models, where regional proteinopathy is more directly characterizable than in patients, better fit with transsynaptic- or extracellular-based theories of pathology spread. We find that, consistently across the datasets used in this study, spatiotemporal amyloid-β pathology patterns are more consistent with extracellular-based explanations of pathology spread. Furthermore, we find that regional levels of amyloid precursor protein in a mouse model are also better correlated with expected pathology patterns based on extracellular, rather than intracellular or transsynaptic spread.http://journal.frontiersin.org/article/10.3389/fneur.2017.00653/fullconnectomicsneurodegenerative diseasesneurodegenerationcomputational modelingproteinopathyamyloid |
| spellingShingle | Chris Mezias Ashish Raj Ashish Raj Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity Frontiers in Neurology connectomics neurodegenerative diseases neurodegeneration computational modeling proteinopathy amyloid |
| title | Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity |
| title_full | Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity |
| title_fullStr | Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity |
| title_full_unstemmed | Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity |
| title_short | Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity |
| title_sort | analysis of amyloid β pathology spread in mouse models suggests spread is driven by spatial proximity not connectivity |
| topic | connectomics neurodegenerative diseases neurodegeneration computational modeling proteinopathy amyloid |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2017.00653/full |
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