Role of the Alzheimer's predisposition factor CD2AP in brain endothelial cells

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atmire.migration.oldid5708
dc.contributor.advisorNguyen, Minh Dang
dc.contributor.authorGunn, Colin
dc.contributor.committeememberGordon, Grant
dc.contributor.committeememberSanati Nezhad, Amir
dc.contributor.committeememberPoulin, Marc
dc.date.accessioned2017-06-23T21:56:47Z
dc.date.available2017-06-23T21:56:47Z
dc.date.issued2017
dc.date.submitted2017en
dc.description.abstractAlzheimer disease (AD) is the most prevalent form of dementia in the elderly. Vascular degeneration plays a critical role in AD pathogenesis. For instance, APOE4 allele, the main genetic risk factor for AD, is linked to reduced cerebral blood flow and increased blood brain barrier (BBB) leakiness. CD2-associated protein (CD2AP) is an adaptor protein that regulates receptor endocytosis and recycling. Two single nucleotide polymorphisms in CD2AP are associated with higher risk for AD and levels of CD2AP are decreased in lymphocytes of sporadic AD patients. Recent human studies also show that CD2AP is linked to the burden of Aβ plaques, memory deficits and modulates AD symptoms in APOE4 patients. Interestingly, CD2AP is enriched in the brain microvascular endothelial cells (BMECs), a key component of the brain microvasculature. However, the basic functions of CD2AP in BMECs and its contribution to brain vasculature dysfunction in AD remain totally unknown. Here we show that siRNA-mediated depletion of CD2AP in both human brain endothelial cell line and mouse primary BMECs leads to the deregulation of proteins involved in AD pathogenesis. Of particular interest, we found that CD2AP interacts with one of these proteins, ApoER2, the receptor for ApoE that is targeted to degradation upon ligation by AD allele ApoE4. Similar to ApoE4, CD2AP loss reduced the levels of ApoER2. Finally, we discovered that downregulation of ApoER2 in CD2AP-depleted cells is modulated by Rab5 GTPase activity.en_US
dc.identifier.citationGunn, C. (2017). Role of the Alzheimer's predisposition factor CD2AP in brain endothelial cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27685en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27685
dc.identifier.urihttp://hdl.handle.net/11023/3903
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBiology--Cell
dc.subjectBiology--Molecular
dc.subjectNeuroscience
dc.subject.otherCD2AP
dc.subject.otherAlzheimer's
dc.subject.otherBrain
dc.titleRole of the Alzheimer's predisposition factor CD2AP in brain endothelial cells
dc.typemaster thesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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