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Apolipoprotein E, amyloid-beta, and blood-brain barrier permeability in Alzheimer disease.

Abstract

There is increasing evidence for blood-brain barrier (BBB) compromise in Alzheimer disease (AD). The presence of the epsilon4 allele of the apolipoprotein E (apoE) gene is a risk factor for sporadic AD. Apolipoprotein E is essential both for maintenance of BBB integrity and for the deposition of fibrillar amyloid-beta (Abeta) that leads to the development of Abeta plaques in AD and to cerebral amyloid angiopathy. This review investigates the relationships between apoE, Abeta, and the BBB in AD. Alterations in the expression and distribution of the BBB Abeta transporters receptor for advanced glycation end-products and low-density lipoprotein receptor-related protein 1 in AD and the potential roles of apoE4 expression in adversely influencing Abeta burden and BBB permeability are also examined. Because both apoE and Abeta are ligands for low-density lipoprotein receptor-related protein 1, all 3 molecules are present in AD plaques, and most AD plaques are located close to the cerebral microvasculature. The interactions of these molecules at the BBB likely influence metabolism and clearance of Abeta and contribute to AD pathogenesis. Therapeutic alternatives targeting apoE/Abeta and sealing a compromised BBB are under development for the treatment of AD.

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  • Authors+Show Affiliations

    ,

    Division of Neuropathology, Department of Pathology, Rhode Island Hospital, Providence, Rhode Island 02903, USA. JDonahue3@Lifespan.org

    Source

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Animals
    Apolipoproteins E
    Blood-Brain Barrier
    Capillary Permeability
    Humans

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Review

    Language

    eng

    PubMed ID

    18379441

    Citation

    Donahue, John E., and Conrad E. Johanson. "Apolipoprotein E, Amyloid-beta, and Blood-brain Barrier Permeability in Alzheimer Disease." Journal of Neuropathology and Experimental Neurology, vol. 67, no. 4, 2008, pp. 261-70.
    Donahue JE, Johanson CE. Apolipoprotein E, amyloid-beta, and blood-brain barrier permeability in Alzheimer disease. J Neuropathol Exp Neurol. 2008;67(4):261-70.
    Donahue, J. E., & Johanson, C. E. (2008). Apolipoprotein E, amyloid-beta, and blood-brain barrier permeability in Alzheimer disease. Journal of Neuropathology and Experimental Neurology, 67(4), pp. 261-70. doi:10.1097/NEN.0b013e31816a0dc8.
    Donahue JE, Johanson CE. Apolipoprotein E, Amyloid-beta, and Blood-brain Barrier Permeability in Alzheimer Disease. J Neuropathol Exp Neurol. 2008;67(4):261-70. PubMed PMID: 18379441.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Apolipoprotein E, amyloid-beta, and blood-brain barrier permeability in Alzheimer disease. AU - Donahue,John E, AU - Johanson,Conrad E, PY - 2008/4/2/pubmed PY - 2008/6/13/medline PY - 2008/4/2/entrez SP - 261 EP - 70 JF - Journal of neuropathology and experimental neurology JO - J. Neuropathol. Exp. Neurol. VL - 67 IS - 4 N2 - There is increasing evidence for blood-brain barrier (BBB) compromise in Alzheimer disease (AD). The presence of the epsilon4 allele of the apolipoprotein E (apoE) gene is a risk factor for sporadic AD. Apolipoprotein E is essential both for maintenance of BBB integrity and for the deposition of fibrillar amyloid-beta (Abeta) that leads to the development of Abeta plaques in AD and to cerebral amyloid angiopathy. This review investigates the relationships between apoE, Abeta, and the BBB in AD. Alterations in the expression and distribution of the BBB Abeta transporters receptor for advanced glycation end-products and low-density lipoprotein receptor-related protein 1 in AD and the potential roles of apoE4 expression in adversely influencing Abeta burden and BBB permeability are also examined. Because both apoE and Abeta are ligands for low-density lipoprotein receptor-related protein 1, all 3 molecules are present in AD plaques, and most AD plaques are located close to the cerebral microvasculature. The interactions of these molecules at the BBB likely influence metabolism and clearance of Abeta and contribute to AD pathogenesis. Therapeutic alternatives targeting apoE/Abeta and sealing a compromised BBB are under development for the treatment of AD. SN - 0022-3069 UR - https://www.unboundmedicine.com/medline/citation/18379441/Apolipoprotein_E_amyloid_beta_and_blood_brain_barrier_permeability_in_Alzheimer_disease_ L2 - https://academic.oup.com/jnen/article-lookup/doi/10.1097/NEN.0b013e31816a0dc8 DB - PRIME DP - Unbound Medicine ER -