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Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice
Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vaso...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399593/ https://www.ncbi.nlm.nih.gov/pubmed/28435465 http://dx.doi.org/10.7150/thno.18509 |
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author | Wiesmann, Maximilian Zerbi, Valerio Jansen, Diane Lütjohann, Dieter Veltien, Andor Heerschap, Arend Kiliaan, Amanda J |
author_facet | Wiesmann, Maximilian Zerbi, Valerio Jansen, Diane Lütjohann, Dieter Veltien, Andor Heerschap, Arend Kiliaan, Amanda J |
author_sort | Wiesmann, Maximilian |
collection | PubMed |
description | Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPP(swe)/PS1(dE9) (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF. Furthermore, using advanced MRI techniques, decline of functional and structural connectivity was revealed in the AD-like mice coupled to impaired cognition, increased locomotor activity, and anxiety-related behavior. Post mortem analyses demonstrated also increased neuroinflammation, and both decreased synaptogenesis and neurogenesis in the AβPP/PS1 mice. Additionally, deviant levels of fatty acids and sterols were present in the brain tissue of the AβPP/PS1 mice indicating maladapted brain fatty acid metabolism. Our findings suggest a link between increased SBP, decreased cerebral hemodynamics and connectivity in an AD mouse model during aging, leading to behavioral and cognitive impairments. As these results mirror the complex clinical symptomatology in the prodromal phase of AD, we suggest that this AD-like murine model could be used to investigate prevention and treatment strategies for early AD patients. Moreover, this study helps to develop more efficient therapies and diagnostics for this very early stage of AD. |
format | Online Article Text |
id | pubmed-5399593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-53995932017-04-21 Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice Wiesmann, Maximilian Zerbi, Valerio Jansen, Diane Lütjohann, Dieter Veltien, Andor Heerschap, Arend Kiliaan, Amanda J Theranostics Research Paper Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPP(swe)/PS1(dE9) (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF. Furthermore, using advanced MRI techniques, decline of functional and structural connectivity was revealed in the AD-like mice coupled to impaired cognition, increased locomotor activity, and anxiety-related behavior. Post mortem analyses demonstrated also increased neuroinflammation, and both decreased synaptogenesis and neurogenesis in the AβPP/PS1 mice. Additionally, deviant levels of fatty acids and sterols were present in the brain tissue of the AβPP/PS1 mice indicating maladapted brain fatty acid metabolism. Our findings suggest a link between increased SBP, decreased cerebral hemodynamics and connectivity in an AD mouse model during aging, leading to behavioral and cognitive impairments. As these results mirror the complex clinical symptomatology in the prodromal phase of AD, we suggest that this AD-like murine model could be used to investigate prevention and treatment strategies for early AD patients. Moreover, this study helps to develop more efficient therapies and diagnostics for this very early stage of AD. Ivyspring International Publisher 2017-03-06 /pmc/articles/PMC5399593/ /pubmed/28435465 http://dx.doi.org/10.7150/thno.18509 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wiesmann, Maximilian Zerbi, Valerio Jansen, Diane Lütjohann, Dieter Veltien, Andor Heerschap, Arend Kiliaan, Amanda J Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice |
title | Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice |
title_full | Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice |
title_fullStr | Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice |
title_full_unstemmed | Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice |
title_short | Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice |
title_sort | hypertension, cerebrovascular impairment, and cognitive decline in aged aβpp/ps1 mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399593/ https://www.ncbi.nlm.nih.gov/pubmed/28435465 http://dx.doi.org/10.7150/thno.18509 |
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