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Secretion of the amyloid precursor protein is elevated isoform specifically by apolipoprotein E4

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Advances in Dementia Research

Abstract

Genetic studies suggest that the neuropathology and etiology of Alzheimer’s disease (AD) are associated with several genotypes including mutations in the amyloid precursor protein (APP) gene and the allele E4 of apolipoprotein E (apoE). The present study investigated the possibility that cross talk interactions exist between APP and apoE and the extent to which they are affected by the apoE genotype. This was pursued by cell culture and immunoblot experiments utilizing neuroblastoma N2a cells in which the effects of distinct apoE isoforms on the levels of intracellular APP and of secreted APPs were determined. This revealed that treatment of the cells with apoE4, the AD risk factor, resulted in a marked increase in the levels of secreted APPs. This effect was dose dependent (ED50 ≅ 2.5μg/ml) and isoform specific in that apoE3 had virtually no effect on the secretion of APPs.

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References

  • Barger SW, Mattson MP (1997) Isoform specific modulation by apolipoprotein E of the activities of secreted β-amyloid precursor protein. J Neurochem 69: 60 – 67

    CAS  Google Scholar 

  • Bellosta S, Nathan BP, Orth M, Dong LM, Mahley RW, Pitas RE (1995) Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth. J Biol Chem 270: 27063 – 27071

    Article  PubMed  CAS  Google Scholar 

  • Caporaso GL, Gandy SE, Buxbaum JP, Ramabhardan TV, Greengard P (1992) Protein phosphorylation regulates secretion of Alzheimer beta/A4 precursor protein. Proc Natl Acad Sci (USA) 89: 3055 – 3059

    Article  CAS  Google Scholar 

  • Corder EH, Saunders AM, Strittmater WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines IL, Pericak-Vance MA (1993) Gene dose of apolipoprotein-E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261: 921 – 923

    Article  PubMed  CAS  Google Scholar 

  • Desdouits-Magnen J, Desdouites F, Takeda S, Syu L-J, Saltiel AR, Bouxbaum JD, Czernik AJ, Neiren AC, Griengard P (1998) Regulation of secretion of Alzheimer amyloid precursor protein by the mitogen-activated protein kinase cascade. J Neurochem 70: 524 – 530

    Article  PubMed  CAS  Google Scholar 

  • Hass S, Fresser F, Kochl S, Beyreuther K, Utermann G, Baier G (1998) Physical interaction of apoE with amyloid precursor protein independent of the amyloid region in vitro. J Biol Chem 273: 13892 – 13897

    PubMed  CAS  Google Scholar 

  • Hilbich C, Monning U, Grund C, Masters CL, Beyreuther K (1993) Amyloid-like properties of peptides flanking the epitope of anyloid precursor protein-specific monoclonal antibody 22C11. J Biol Chem 268: 26571 – 26577

    PubMed  CAS  Google Scholar 

  • Levy-Lahad E, Wasco W, Poovkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K, Crowley AC, Fu Y-H, Guenette Y, Galas D, Nemens E, Wijman EM, Bird TD, Schellenberg GD, Tanzi RE (1995) Candidate gene for the chronosome L familial Alzheimer’s disease locus. Science 269: 973 – 977

    Article  PubMed  CAS  Google Scholar 

  • Mhley RW (1988) Apolipoprotein E cholesterol transport protein with expanding role in cell biology. Science 240: 622 – 630

    Google Scholar 

  • Masters CL, Beyreuther K (1998) Alzheimer’s disease. Br Med J 316: 446 – 448

    CAS  Google Scholar 

  • Miyata M, Smith JD (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet 14 (1): 55 – 61

    CAS  Google Scholar 

  • Muller W, Meske V, Berlin K, Scharnagl H, Marz H, Ohm TG (1998) Apolipoprotein E isoforms increase intracellular Ca2+ differentially through a ω-agatoxin IVa-sensitive Ca2+-channel. Brain Pathol 8: 641 – 653

    Article  PubMed  CAS  Google Scholar 

  • Nitsch RM, Slack BE, Wutrman RJ, Growdon JA (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258: 304 – 307

    Article  PubMed  CAS  Google Scholar 

  • Roses AD (1996) Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Ann Rev Med 47: 387 - 400

    CAS  Google Scholar 

  • Saunders AM, Strittmatter WJ, Schmechel D, St George-Hyslop PH, Piricak-Vance MA, Joo SH, Rosi B A, Grisella JF, Crapper-Machachlan DR, Alpats MJ, Hulette C, Crain B, Goldgaber D, Roses AD (1993) Association of apolipoprotein-E allele E4 with late onset familial sporadic Alzheimer’s disease. Neurology 43: 1467 – 1472

    PubMed  CAS  Google Scholar 

  • Selkoe DS (1998) The cell biology of beta-amyloid precursor protein and presenilins in Alzheimer’s disease. Trends Cell Biol 8: 447 – 453

    Article  PubMed  CAS  Google Scholar 

  • Sherrington R, Rogaeva EI, Liang Y, Rogaeva EA, Levesque E, Ikeda M, Chi H, Lin C, Li G, Holman K (1995) Cloning of a gene bearing missense mutations in early onset familial Alzheimer’s disease. Nature 375: 754 – 760

    Article  PubMed  CAS  Google Scholar 

  • Slake BE, Nitsch RM, Livne E, Kunz GM, Eldar N, Wurtman RJ (1993) Regulation of amyloid precursor protein release by protein kinase C in Swiss 3T3 fibroblasts. Ann N Y Acad Sci 695: 128 – 131

    Article  Google Scholar 

  • Wolozin BL, Basaric-Keys J, Canter R, Li Y, Vanderputten D, Sunderland T (1996) Differential regulation of APP secretion in apolipoprotein E3 and E4. Ann N Y Acad Sci 777: 322 – 326

    Article  PubMed  CAS  Google Scholar 

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© 2000 Springer-Verlag

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Oron, L., Efrati, M., Michaelson, D.M. (2000). Secretion of the amyloid precursor protein is elevated isoform specifically by apolipoprotein E4. In: Jellinger, K., Schmidt, R., Windisch, M. (eds) Advances in Dementia Research. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6781-6_18

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  • DOI: https://doi.org/10.1007/978-3-7091-6781-6_18

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83512-8

  • Online ISBN: 978-3-7091-6781-6

  • eBook Packages: Springer Book Archive

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