Quantification of molecular interactions between ApoE, amyloid-beta (Aβ) and laminin: Relevance to accumulation of Aβ in Alzheimer's disease

Biochimica Et Biophysica Acta
Jurgita ZekonyteR O Carare

Abstract

Accumulation of amyloid-β (Aβ) in plaques in the brain and in artery walls as cerebral amyloid angiopathy indicates a failure of elimination of Aβ from the brain with age and Alzheimer's disease. A major pathway for elimination of Aβ and other soluble metabolites from the brain is along basement membranes within the walls of cerebral arteries that represent the lymphatic drainage pathways for the brain. The motive force for the elimination of Aβ along this perivascular pathway appears to be the contrary (reflection) wave that follows the arterial pulse wave. Following injection into brain parenchyma, Aβ rapidly drains out of the brain along basement membranes in the walls of cerebral arteries; such drainage is impaired in apolipoprotein E ε4 (ApoE4) mice. For drainage of Aβ to occur in a direction contrary to the pulse wave, some form of attachment to basement membrane would be required to prevent reflux of Aβ back into the brain during the passage of the subsequent pulse wave. In this study, we show first that apolipoprotein E co-localizes with Aβ in basement membrane drainage pathways in the walls of arteries. Secondly, we show by Atomic Force Microscopy that attachment of ApoE4/Aβ complexes to basement membrane laminin is si...Continue Reading

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Citations

Feb 28, 2016·Biochimica Et Biophysica Acta·M Paul MurphyDonna M Wilcock
Jan 17, 2017·Nature Immunology·Britta EngelhardtRoy O Weller
Apr 9, 2017·Journal of Lipid Research·Leon M TaiMary Jo LaDu
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Mar 21, 2019·BMC Medicine·Mirna SafiehDaniel M Michaelson
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Feb 12, 2019·Frontiers in Aging Neuroscience·Roxana AldeaGiles Richardson
Dec 18, 2020·Frontiers in Physiology·Matthew D HoweAkihiko Urayama

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