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

Jurgita Zekonyte, Kenji Sakai, James A.R. Nicoll, Roy O. Weller, Roxana O. Carare

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    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 significantly weaker than ApoE3/Aβ complexes. These results suggest that perivascular elimination of ApoE4/Aβ 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/Aβ/laminin interactions may increase the efficiency of elimination of Aβ in the prevention of Alzheimer's disease.
    Original languageEnglish
    Pages (from-to)1047-1053
    JournalBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
    Volume1862
    Issue number5
    Early online date29 Aug 2015
    DOIs
    Publication statusPublished - May 2016

    Keywords

    • Apolipoprotein E
    • atomic force microscopy
    • perivascular clearance pathways
    • Alzheimer's disease
    • laminin
    • WNU

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