Quantification of molecular interactions between apoE, Amyloid-beta (A?) and laminin: Relevance to accumulation of A? in Alzheimer’s disease

Accumulation of amyloid-? (A?) in plaques in the brain and in artery walls as cerebral amyloid angiopathy indicates a failure of elimination of A? from the brain with age and Alzheimer’s disease. A major pathway for elimination of A? 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 A? along this perivascular pathway appears to be the contrary (reflection) wave that follows the arterial pulse wave. Following injection into brain parenchyma, A? rapidly drains out of the brain along basement membranes in the walls of cerebral arteries; such drainage is impaired in apolipoprotein E ?4 (ApoE4) mice. For drainage of A? to occur in a direction contrary to the pulse wave some form of attachment to basement membrane would be required to prevent reflux of A? back into the brain during the passage of the subsequent pulse wave. In this study, the authors show first that apolipoprotein E co-localises with A? in basement membrane drainage pathways in the walls of arteries. Secondly, the authors show by Atomic Force Microscopy that attachment of ApoE4/A? complexes to basement membrane laminin is significantly weaker than ApoE3/A? complexes. These results suggest that perivascular elimination of ApoE4/A? complexes would be less efficient than with other isoforms of apolipoprotein E, thus endowing a higher risk for Alzheimer’s disease. Therapeutic correction for ApoE4/A?/laminin interactions may increase the efficiency of elimination of A? in the prevention of Alzheimer’s disease.

Authors: Zekonyte J, Sakai K, Nicoll JA, Weller RO, Carare RO. ;Full Source: Biochim Biophys Acta. 2015 Aug 28. pii: S0925-4439(15)00262-8. doi: 10.1016/j.bbadis.2015.08.025. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Epub ahead of print] ;[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]