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Vascular Transport of Alzheimer’s Amyloid β Peptides and Apolipoproteins

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Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders

Abstract

Deposition of amyloid β (Aβ) in the central nervous system (CNS) occurs during normal aging and is accelerated by Alzheimer’s disease. Aβ accumulation in the CNS is considered a central part in the pathogenesis of Alzheimer’s disease. Recent studies from our laboratory and other laboratories suggest a major role of the blood-brain barrier (BBB) in determining the concentrations of Aβ in the CNS. The BBB has a dual role: i) to control the entry of plasma-derived Aβ and it’s binding transport proteins into the CNS, and ii) to regulate the levels of brain-derived Aβ via clearance mechanisms. Using in vivo rodent and non-human primate models, and an in vitro model of the human BBB, we have demonstrated transcytosis of plasma-derived Aβ1–40 and Aβ1–42 across the BBB suggesting that putative AD receptors in brain endothelial cells, e.g., the ‘receptor for advanced glycation end products’ (RAGE), scavenger receptor (SR), and lipoprotein receptors, e.g., gp330/megalin and possibly other members of the low density lipoprotein (LDL) receptor family, may regulate the BBB transport of Aβ free and/or complexed to apolipoproteins J and E (ApoJ, ApoE). Since ApoJ and ApoE receptors, and AD putative receptors/transporters are potential drug targets, understanding their function in vivo and in vitro in different animal and human models may help developing strategies to prevent and/or decelerate brain accumulation of AD, amyloid formation and associated cytotoxic effects. In this chapter we will discuss the role of vascular CNS transport of Aβ and its binding apolipoproteins in relation to its importance in the development of brain amyloidosis and AD pathology.

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Authors and Affiliations

  1. Department of Neurological Surgery, USC School of Medicine, Los Angeles, CA, USA

    Berislav V. Zlokovic

  2. Department of Pathology, New York University Medical Center, New York, NY, 10016, USA

    Jorge Ghiso & Blas Frangione

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  1. Departments of Neurology and Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands

    Marcel M. Verbeek

  2. Department of Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands

    Robert M. W. de Waal

  3. UCLA Medical Center, Los Angeles, CA, USA

    Harry V. Vinters

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Zlokovic, B.V., Ghiso, J., Frangione, B. (2000). Vascular Transport of Alzheimer’s Amyloid β Peptides and Apolipoproteins. In: Verbeek, M.M., de Waal, R.M.W., Vinters, H.V. (eds) Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1007-7_20

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