Amyloid-β Aggregation Propensity and Toxicity to Cerebrovascular Smooth Muscle Cells: The Influence of Carboxy Terminal Length and Interaction with Apolipoprotein E

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dc.contributor.advisorWevers, R.
dc.contributor.advisorVerbeek, M.
dc.contributor.authorDirven, Bart
dc.date.issued2015-06-25
dc.description.abstractThe pathology of Alzheimer’s disease (AD) is characterized by the deposition of amyloid beta (Aβ) plaques in brain tissue and vasculature. Vascular deposition of Aβ, called amyloid angiopathy (CAA), leads to degeneration of cells surrounding the blood-brain barrier. The severity of Aβ cytotoxicity is likely influenced by multiple factors, including the carboxy terminal length of the peptide and its interaction with the apolipoprotein E (ApoE) protein. We have studied how both these factors influence Aβ aggregation propensity and Aβ toxicity in cerebrovascular smooth muscle cells (CVSMCs). We found that both increased carboxy terminal length and the presence of ApoE markedly increased Aβ aggregation propensity. Additionally, it was found that both shorter (Aβ38) and longer (Aβ43) Aβ species showed relatively increased short-term toxicity to CVSMCs, in contrast to the intermediate-length Aβ40. ApoE3 reduced cytotoxicity of Aβ38, Aβ40 and AβD40 in a concentration-dependent fashion. Interestingly, Aβ43 toxicity did not seem to be influenced by the addition of ApoE3. We conclude that the relationship between Aβ aggregation propensity and toxicity to CVSMCs is non-linear, as Aβ peptides with both high (Aβ43) and low (Aβ38) aggregation propensity exerted a substantial toxic effect on CVSMCs, as opposed to Aβ peptides with intermediate aggregation propensity like Aβ40. We think these data will contribute to our understanding of how the properties of the Aβ peptide and its interaction with ApoE influence Aβ pathology in AD and CAA.en_US
dc.embargo.lift2040-06-25
dc.identifier.urihttp://theses.ubn.ru.nl/handle/123456789/4113
dc.language.isoenen_US
dc.thesis.facultyFaculteit der Sociale Wetenschappenen_US
dc.thesis.specialisationResearchmaster Cognitive Neuroscienceen_US
dc.thesis.studyprogrammeResearchmaster Cognitive Neuroscienceen_US
dc.thesis.typeResearchmasteren_US
dc.titleAmyloid-β Aggregation Propensity and Toxicity to Cerebrovascular Smooth Muscle Cells: The Influence of Carboxy Terminal Length and Interaction with Apolipoprotein Een_US
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