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The role of lipoproteins on selected functions relevant to Alzheimer's Disease in human brain perivascular cells Soo, Sonja Kar Yee
Abstract
Alzheimer‘s Disease (AD) is a progressive neurodegenerative disease that affects millions of people world-wide. It is characterized by amyloid plaques and neurofibrillary tangles in the brain. Many AD patients also show loss of cerebrovascular integrity, which is thought to lead to decreased capillary flow, neuronal injury and impaired clearance of amyloid beta. Since apolipoprotein E (apoE) and high density lipoprotein (HDL) show many beneficial effects in the vasculature in the body, we aimed to test the effects of these lipoproteins on primary human perivascular cells in the brain. We found that pharmacologically increasing apoE levels with GW3965 in a scratch-wound assay was not associated with changes in pericyte migration. Interestingly, we found that Axl inhibitor A1 slowed pericyte migration without showing changes in secreted apoE levels, suggesting an apoE-independent pathway for pericyte migration. We also tested whether HDL can attenuate the CypA-NFκB-MMP9 inflammatory pathway associated with apoE4 pericytes, but failed to observe the activation of this inflammatory pathway in our pericytes. Lastly, we found that when macrophages were treated with HDL, Aβ phagocytosis was not changed. Moreover, there were donor differences in the inflammatory response of macrophages to Aβ, making consistent observations difficult. Taken together, we did not show beneficial effects of lipoproteins on perivascular cell function in the context of AD.
Item Metadata
Title |
The role of lipoproteins on selected functions relevant to Alzheimer's Disease in human brain perivascular cells
|
Creator | |
Publisher |
University of British Columbia
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Date Issued |
2018
|
Description |
Alzheimer‘s Disease (AD) is a progressive neurodegenerative disease that affects millions of
people world-wide. It is characterized by amyloid plaques and neurofibrillary tangles in the
brain. Many AD patients also show loss of cerebrovascular integrity, which is thought to lead to
decreased capillary flow, neuronal injury and impaired clearance of amyloid beta. Since
apolipoprotein E (apoE) and high density lipoprotein (HDL) show many beneficial effects in the
vasculature in the body, we aimed to test the effects of these lipoproteins on primary human
perivascular cells in the brain. We found that pharmacologically increasing apoE levels with
GW3965 in a scratch-wound assay was not associated with changes in pericyte migration.
Interestingly, we found that Axl inhibitor A1 slowed pericyte migration without showing
changes in secreted apoE levels, suggesting an apoE-independent pathway for pericyte
migration. We also tested whether HDL can attenuate the CypA-NFκB-MMP9 inflammatory
pathway associated with apoE4 pericytes, but failed to observe the activation of this
inflammatory pathway in our pericytes. Lastly, we found that when macrophages were treated
with HDL, Aβ phagocytosis was not changed. Moreover, there were donor differences in the
inflammatory response of macrophages to Aβ, making consistent observations difficult. Taken
together, we did not show beneficial effects of lipoproteins on perivascular cell function in the
context of AD.
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Genre | |
Type | |
Language |
eng
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Date Available |
2019-06-30
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0368620
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2018-09
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International