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Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease.

Abstract

The effect of the apolipoprotein E genotype on the development of late onset Alzheimer's disease is still debated. Neuropathological studies of Alzheimer's disease have found a great extent of amyloid deposition in cortex and blood vessel walls in association with the apolipoprotein E epsilon 4 genotype [Rebeck G. W. et al. (1993) Neuron 11, 575-580; Schmechel et al. (1993) Proc. natn. Acad. Sci. U.S.A. 90, 9649-9653]. In contrast, the relationship of apolipoprotein E genotype to neurofibrillary pathology in Alzheimer's disease has been less clear. In this study we present evidence on the influence of the apolipoprotein E genotype on Alzheimer's disease related pathology in a series of 76 autopsy cases that had pathology that fulfilled the CERAD criteria for Alzheimer's disease. We found that the presence of the apolipoprotein E epsilon 4 allele is correlated with increased amounts of both amyloid and neuritic pathology in the neocortex as determined using an image analysis system. Comparison of plaque and tangle densities with the allele doses of epsilon 2 and epsilon 4 revealed a striking parallelism, suggesting that the alleles exert their effects very early in the pathological process before deposition of plaques and tangles. Although the apolipoprotein E epsilon 2 allele had a protective effect against both amyloid deposition and neurofibrillary tangle formation, in the presence of the epsilon 4 allele this protective effect against neuritic pathology was less marked than against amyloid deposition. This differential effect on amyloid deposition and the accumulation of neuritic pathology suggests that different molecular mechanisms are involved in the effect of apolipoprotein E on amyloid deposition and on tau phosphorylation.

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  • Authors+Show Affiliations

    ,

    Oxford Project to Investigate Memory and Ageing (OPTIMA), Radcliffe Infirmary NHS Trust, Oxford, U.K.

    , , , , ,

    Source

    Neuroscience 69:3 1995 Dec pg 757-61

    MeSH

    Aged
    Aged, 80 and over
    Alleles
    Alzheimer Disease
    Amyloid
    Apolipoprotein E2
    Apolipoprotein E3
    Apolipoprotein E4
    Apolipoproteins E
    Female
    Genotype
    Humans
    Male
    Middle Aged
    Neurites
    Neurofibrillary Tangles

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    8596645

    Citation

    Nagy, Z, et al. "Influence of the Apolipoprotein E Genotype On Amyloid Deposition and Neurofibrillary Tangle Formation in Alzheimer's Disease." Neuroscience, vol. 69, no. 3, 1995, pp. 757-61.
    Nagy Z, Esiri MM, Jobst KA, et al. Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease. Neuroscience. 1995;69(3):757-61.
    Nagy, Z., Esiri, M. M., Jobst, K. A., Johnston, C., Litchfield, S., Sim, E., & Smith, A. D. (1995). Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease. Neuroscience, 69(3), pp. 757-61.
    Nagy Z, et al. Influence of the Apolipoprotein E Genotype On Amyloid Deposition and Neurofibrillary Tangle Formation in Alzheimer's Disease. Neuroscience. 1995;69(3):757-61. PubMed PMID: 8596645.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer's disease. AU - Nagy,Z, AU - Esiri,M M, AU - Jobst,K A, AU - Johnston,C, AU - Litchfield,S, AU - Sim,E, AU - Smith,A D, PY - 1995/12/1/pubmed PY - 1995/12/1/medline PY - 1995/12/1/entrez SP - 757 EP - 61 JF - Neuroscience JO - Neuroscience VL - 69 IS - 3 N2 - The effect of the apolipoprotein E genotype on the development of late onset Alzheimer's disease is still debated. Neuropathological studies of Alzheimer's disease have found a great extent of amyloid deposition in cortex and blood vessel walls in association with the apolipoprotein E epsilon 4 genotype [Rebeck G. W. et al. (1993) Neuron 11, 575-580; Schmechel et al. (1993) Proc. natn. Acad. Sci. U.S.A. 90, 9649-9653]. In contrast, the relationship of apolipoprotein E genotype to neurofibrillary pathology in Alzheimer's disease has been less clear. In this study we present evidence on the influence of the apolipoprotein E genotype on Alzheimer's disease related pathology in a series of 76 autopsy cases that had pathology that fulfilled the CERAD criteria for Alzheimer's disease. We found that the presence of the apolipoprotein E epsilon 4 allele is correlated with increased amounts of both amyloid and neuritic pathology in the neocortex as determined using an image analysis system. Comparison of plaque and tangle densities with the allele doses of epsilon 2 and epsilon 4 revealed a striking parallelism, suggesting that the alleles exert their effects very early in the pathological process before deposition of plaques and tangles. Although the apolipoprotein E epsilon 2 allele had a protective effect against both amyloid deposition and neurofibrillary tangle formation, in the presence of the epsilon 4 allele this protective effect against neuritic pathology was less marked than against amyloid deposition. This differential effect on amyloid deposition and the accumulation of neuritic pathology suggests that different molecular mechanisms are involved in the effect of apolipoprotein E on amyloid deposition and on tau phosphorylation. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/8596645/Influence_of_the_apolipoprotein_E_genotype_on_amyloid_deposition_and_neurofibrillary_tangle_formation_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/030645229500331C DB - PRIME DP - Unbound Medicine ER -