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The role of lipoproteins on selected functions relevant to Alzheimer's Disease in human brain perivascular cells

University of British Columbia

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.

Text

2019-06-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/66288

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/