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ApoE and Aβ1–42 interactions

Effects of isoform and conformation on structure and function

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Abstract

Abnormalities in the processing of amyloid precursor protein to amyloid-β (Aβ) are causal factors, and the presence of the ε4 allele of apolipoprotein E (apoE) is the primary risk factor for Alzheimer’s disease (AD). Based, at least in part, on these genetics, the potential structural and functional interactions between these two proteins are the focus of our research. To understand the nature of the physical interactions between apoE and Aβ, we initially utilized gel-shift assays to demonstrate that native apoE2 and E3 (associated with lipid particles) form an SDS-stable complex with Aβ that is more abundant than the apoE4:Aβ complex. We further demonstrated that exogenous apoE3 but not E4 prevents Aβ-induced neurotoxicity by a process that requires apoE receptors. In addition, both exogenous apoE3 and E4 prevent Aβ-induced, glial-mediated inflammation, also via a process that requires apoE receptors. These functional effects all occur at a molar ratio of apoE to Aβ of 1:30. Because the biological activities for both apoE and Aβ are profoundly influenced by their isoform and conformation, respectively, we further investigated the idea that apoE3 and E4 differentially interact with particular aggregation species of Aβ1–42. Our overall hypothesis is that apoE has two general functions in relation to Aβ. First, apoE interacts with oligomeric Aβ via an apoE receptor-mediated process to inhibit neurotoxicity and neuroinflammation (apoE3>apoE4) a process possibly related to binding and clearance of apoE3:oligomer complexes. Second, apoE facilitates the deposition of Aβ as amyloid (apoE4 \s>apoE3). We will continue to investigate the effect of apoE isoform and Aβ conformation on the structural and functional interactions between these two proteins in relation to the pathogenesis of AD.

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References

  • Aleshkov S., Abraham C. R., and Zannis V. I. (1997) Interaction of nascent apoE2, apoE3, and apoE4 isoforms expressed in mammalian cells with amyloid peptide β(1–40): relevance to Alzheimer’s disease. Biochemistry 36, 10571–10580.

    Article  PubMed  CAS  Google Scholar 

  • Bales K. R., Verina T., Dodel R. C., Du Y., Altstiel L., Bender, M., et al. (1997) Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition. Nat. Genet. 17, 263,264.

    Article  PubMed  CAS  Google Scholar 

  • Barger S. W. and Harmon A. D. (1997) Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature 388, 878–881.

    Article  PubMed  CAS  Google Scholar 

  • Barger S. W. and Mattson M. P. (1997) Isoform-specific modulation by apolipoprotein E of the activities of secreted β-amyloid precursor protein. J. Neurochem. 69, 60–67.

    Article  PubMed  CAS  Google Scholar 

  • Beffert, U., Aumont N., Dea D., Lussier-Cacan S., Davignon J., and Poirier J. (1999) A polipoprotein E isoformspecific reduction of extracellular amyloid in neuronal cultures. Mol. Brain Res. 68, 181–185.

    Article  PubMed  CAS  Google Scholar 

  • Chartier-Harlin M. C., Parfitt M., Legrain S., Perez-Tur J., Brousseau T., Evans A., et al. 1994. Apolipoprotein E, ε4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer’s disease: analysis of the 19q13.2 chromosomal region. Hum. Mol. Genet. 3, 569–574.

    Article  PubMed  CAS  Google Scholar 

  • Choi-Miura, N. H., Ihara Y., Fukuchi K., Takeda M., Nakano Y., Tobe T., and Tomita M. (1992) SP-40,40 is a constituent of Alzheimer’s amyloid. Acta Neuropathol. 83, 260–264.

    Article  PubMed  CAS  Google Scholar 

  • Chui D. H., Tanahashi H., Ozawa K., Ikeda S., Checler F., Ueda O., et al. (1999) Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat. Med. 5, 560–564.

    Article  PubMed  CAS  Google Scholar 

  • Cole G. M. and. Ard M. D. (2000) Influence of lipoproteins on microglial degradation of Alzheimer’s amyloid beta-protein. Microsc. Res. Tech. 50, 316–24.

    Article  PubMed  CAS  Google Scholar 

  • Cole G. M., Beech W., Frautschy S. A., Sigel J., Glasgow C., and Ard M. D. (1999) Lipoprotein effects on Abeta accumulation and degradation by microglia in vitro. J. Neurosci. Res. 57, 504–520.

    Article  PubMed  CAS  Google Scholar 

  • Corder E. H., Saunder S. M., Risch N. J., Strittmatter W. J., Schmechel D. E., Gaskell P. C. Jr., et al. (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat. Genet. 7, 180–184.

    Article  PubMed  CAS  Google Scholar 

  • Corder E. H., Saunder S. M., Strittmatter W. J., Schmechel D. E., Gaskell P. C., Small G. W., et al. (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 

  • Cummings B. J. and Cotman C. W. (1995) Image analysis of beta-amyloid load in Alzheimer’s disease and relation to dementia severity. Lancet 346, 1524–1528.

    Article  PubMed  CAS  Google Scholar 

  • Dahlgren K. N., Manelli A. M., Stine W. B. Jr., Baker L. K., Krafft G. A., and LaDu M. J. (2002) Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J. Biol. Chem. 277, 32046–32053.

    Article  PubMed  CAS  Google Scholar 

  • Drouet B., Fifre A., Pincon-Raymond M., Vandekerckhove J., Rosseneu M., Gueant J. L., et al. (2001) ApoE protects cortical neurones against neurotoxicity induced by the non-fibrillar C-terminal domain of the amyloid-beta peptide. J. Neurochem. 76, 117–127.

    Article  PubMed  CAS  Google Scholar 

  • Evans K. C., Berger E. P., Cho C. G., Weisgraber K. H., and Lansbury P. T. (1995) Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: implications for the pathogenesis and treatment of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 92, 763–767.

    Article  PubMed  CAS  Google Scholar 

  • Frisoni G. B., Govoni S., Geroldi C., Bianchetti A., Calabresi L., Franceschini G., and Trabucchi M. (1995) Gene dose of the epsilon 4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzheimer’s disease. Ann. Neurol. 37, 596–604.

    Article  PubMed  CAS  Google Scholar 

  • Ghiso J., Matsubara E., Koudinov A., Choi-Miura N. H., Tomita M., Wisniewski T., and Frangione B. (1993) The cerebrospinal-fluid form of Alzheimer’s amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex. Biochem. J. 293, 27–30.

    PubMed  CAS  Google Scholar 

  • Guillaume D., Bertrand P., Dea D., Davignon J., and Poirier J. (1996) Apolipoprotein E and low-density lipoprotein binding and internalization in primary cultures of rat astrocytes: isoform-specific alterations. J. Neurochem. 66, 2410–2418.

    Article  PubMed  CAS  Google Scholar 

  • Haass C. and Steiner H. (2001) Protofibrils, the unifying toxic molecule of neurodegenerative disorders? Nat. Neurosci. 4, 859,860.

    Article  PubMed  CAS  Google Scholar 

  • Hardy J. and Selkoe D. J. (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356.

    Article  PubMed  CAS  Google Scholar 

  • Hartley D. M., Walsh D. M., Ye C. P., Diehl T., Vasquez S., Vassilev P. M., et al. (1999) Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J. Neurosci. 19, 8876–8884.

    PubMed  CAS  Google Scholar 

  • Hartman R. E., Laurer H., Longhi L., Bales K. R., Paul S. M., McIntosh T. K., and Holtzman D. M. (2002) Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer’s disease. J. Neurosci. 22, 10083–10087.

    PubMed  CAS  Google Scholar 

  • Holtzman D. M., Bales K. R., Tenkova T., Fagan A. M., Parsadanian M., Sartorius L. J., et al. (2000) Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 97, 2892–2897.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman D. M., Bales K. R., Wu S., Bhat P., Parsadanian M., Fagan A. M., et al. (1999) In vivo expression of apolipoprotein E reduces amyloid-β deposition in a mouse model of Alzheimer’s disease. J. Clin. Invest. 103, R15-R21.

    PubMed  CAS  Google Scholar 

  • Houlden H., Crook R., Duff K., Collinge J., Roques P., Rossor M., and Hardy J. (1993) Confirmation that the ApoE4 allele is associated with late onset, familial Alzheimer’s disease. Neurodegeneration 2, 283–286.

    Google Scholar 

  • Hu J.. LaDu M. J, and Van Eldik L. J. (1998) Apolipoprotein E attenuates beta-amyloid-induced astrocyte activation. J. Neurochem. 71, 1626–1634.

    Article  PubMed  CAS  Google Scholar 

  • Irizarry M. C., Cheung B. S., Rebeck G. W., Paul S. M., Bales K. R., and Hyman B. T. (2000) Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP (V717F) transgenic mice. Acta Neuropathol. (Berl.) 100, 451–458.

    Article  CAS  Google Scholar 

  • Irizarry M. C., Soriano F., McNamara M., Page K. J., Schenk D., Games D., and Hyman B. T. (1997) Aβ deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J. Neurosci. 17, 7053–7059.

    PubMed  CAS  Google Scholar 

  • Jordán J., Galindo M. F., Miller R. J., Reardon C. A., Getz G. S., and LaDu M. J. (1998) Isoform-specific effect of apolipoprotein E on cell survival and β-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures. J. Neurosci. 18, 195–204.

    PubMed  Google Scholar 

  • Klein W. L., Krafft G. A., and Finch C. E. (2001) Targeting small Abeta oligomers: the solution to an Alzheimer’s disease conundrum? Trends Neurosci. 24, 219–224.

    Article  PubMed  CAS  Google Scholar 

  • Kuo Y. M., Emmerling M. R., Vigo-Pelfrey C., Kasunic T. C., Kirkpatrick J. B., Murdoch G. H., et al. (1996) Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J. Biol. Chem. 271, 4077–81.

    Article  PubMed  CAS  Google Scholar 

  • LaDu M. J., Falduto M. T., Manelli A. M., Reardon C. A., Getz G. S., and Frail D. E. (1994) Isoform-specific binding of apolipoprotein E to β-amyloid. J. Biol. Chem. 269, 23404–23406.

    Google Scholar 

  • LaDu M. J., Lukens J. R., Reardon C. A., and Getz G. S. (1997) Association of human, rat, and rabbit apolipoprotein E with beta-amyloid. J. Neurosci. Res. 49, 9–18.

    Article  PubMed  CAS  Google Scholar 

  • LaDu M. J., Pederson T. M., Frail D. E., Reardon C. A., Getz G. S., and Falduto M. T. (1995) Purification of apolipoprotein E attenuates isoform-specific binding to β-amyloid. J. Biol. Chem. 270, 9030–9042.

    Google Scholar 

  • LaDu M. J., Shah J. A., Reardon C. A., Getz G. S., Bu G., Hu J., et al. (2000) Apolipoprotein E receptors mediate the effects of beta-amyloid on astrocyte cultures. J. Biol. Chem. 275, 33974–33980.

    Article  PubMed  CAS  Google Scholar 

  • LaDu M. J., Shah J. A., Reardon C. A., Getz G. S., Bu G., Hu J., et al. (2001) Apolipoprotein E and apolipoprotein E receptors modulate A beta-induced glial neuroinflammatory responses. Neurochem. Int. 39, 427–434.

    Article  PubMed  CAS  Google Scholar 

  • Lambert M. P., Barlow A. K., Chromy B. A., Edwards C., Freed R., Liosatos M., et al. (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. USA 95, 6448–6453.

    Article  PubMed  CAS  Google Scholar 

  • Lansbury P. T. Jr. (1999) Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc. Natl. Acad. Sci. USA 96, 3342–3344.

    Article  PubMed  CAS  Google Scholar 

  • Laskowitz D. T., Goel S., Bennett E. R., and Matthew W. D. (1997) Apolipoprotein E suppresses glial cell secretion of TNF alpha. J. Neuroimmunol. 76, 70–74.

    Article  PubMed  CAS  Google Scholar 

  • Laskowitz, D. T., Matthew W. D., Bennett E. R., Schmechel D., Herbstreith M. H., Goel S., and McMillian M. K. (1998) Endogenous apolipoprotein E suppresses LPS-stimulated microglial nitric oxide production. Neuroreport 9, 615–618.

    Article  PubMed  CAS  Google Scholar 

  • Lue L. F., Kuo Y. M., Roher A. E., Brachova L., Shen Y., Sue L., et al. (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am. J. Pathol. 155, 853–862.

    PubMed  CAS  Google Scholar 

  • Lynch, J. R., Morgan D., Mance J., Matthew W. D., and Laskowitz D. T. (2001) Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response. J. Neuroimmunol. 114, 107–113.

    Article  PubMed  CAS  Google Scholar 

  • Ma J., Brewer H. B. Jr., and Potter H. (1996) Alzheimer A beta neurotoxicity: promotion by antichymotrypsin, ApoE4; inhibition by A beta-related peptides. Neurobiol. Aging 17, 773–780.

    Article  PubMed  CAS  Google Scholar 

  • Ma J., Yee A., Brewer H. B., Das S., and Potter H. (1994) Amyloid-associated proteins alpha-1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 372, 92–94.

    Article  PubMed  CAS  Google Scholar 

  • Mak Y. T., Chiu H., Woo J., Kay R., Chan Y. S., Hui E., et al. (1996) Apolipoprotein E genotype and Alzheimer’s disease in Hong Kong elderly Chinese. Neurology 46, 146–149.

    PubMed  CAS  Google Scholar 

  • Matsubara E., Frangione B., and Ghiso J. (1995) Characterization of apolipoprotein J-Alzheimer’s Aβ interaction. J. Biol. Chem. 270, 7563–7567.

    Article  PubMed  CAS  Google Scholar 

  • McLean C. A., Cherny R. A., Fraser F. W., Fuller S. J., Smith M. J., Beyreuther K., et al. (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann. Neurol. 46, 860–866.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Mouchel Y., Lefrancois T., Fages C., and Tardy M. (1995) Apolipoprotein E expression in astrocytes: developmental pattern and regulation. Neuroreport 7, 205–208.

    PubMed  CAS  Google Scholar 

  • Namba Y., Tomonaga M., Kawasaki H., Otomo E., and Ikeda K. (1991) Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease kuru plaque amyloid in Creutzfeldt-Jacob disease. Brain Res. 541, 163–166.

    Article  PubMed  CAS  Google Scholar 

  • Naslund J., Haroutunian V., Mohs R., Davis K. L., Davies P., Greengard P., and Buxbaum J. D. (2000) Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA 283, 1571–1577.

    Article  PubMed  CAS  Google Scholar 

  • Oda, T., Wals P., Osterburg H. H., Johnson S. A., Pasinetti G. M., Morgan T. E., et al. (1995) Clusterin (apoJ) alters the aggregation of amyloid beta-peptide (A beta 1-42) and forms slowly sedimenting A beta complexes that cause oxidative stress. Exp. Neurol. 136, 22–31.

    Article  PubMed  CAS  Google Scholar 

  • Pericak-Vance M. A., Johnson C. C., Rimmler J. B., Saunders A. M., Robinson L. C., D’Hondt E. G., et al. (1996) Alzheimer’s disease and apolipoprotein E-4 allele in an Amish population. Ann. Neurol. 39, 700–704.

    Article  PubMed  CAS  Google Scholar 

  • Rebeck G. W., Reiter J. S, Strickland D. K., and Hyman B. T. (1993) Apolipoprotein E in sporadic Alzheimer’s disease: allelic variation and receptor interactions. Neuron 11, 575–580.

    Article  PubMed  CAS  Google Scholar 

  • Roher A. E., Baudry J., Chaney M. O., Kuo Y. M., Stine W. B., and Emmerling M. R. (2000) Oligomerization and fibril assembly of the amyloid-beta protein. Biochim. Biophys. Acta 1502, 31–43.

    PubMed  CAS  Google Scholar 

  • Roher A. E., Chaney M. O., Kuo Y. M., Webster S. D., Stine W. B., Haverkamp L. J., et al. (1996) Morphology and toxicity of Abeta-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer’s disease. J. Biol. Chem. 271, 20631–20635.

    Article  PubMed  CAS  Google Scholar 

  • Royston M. C., Mann D., Pickering-Brown S., Owen F., Perry R., Raghavan R., et al. 1994 Apolipoprotein E epsilon 2 allele promotes longevity and protects patients with Down’s syndrome from dementia. Neuroreport 5, 2583–2585.

    Article  PubMed  CAS  Google Scholar 

  • Sanan D. A., Weisgraber K. H., Russel S. J., Mahley R. W., Huang D., Saunders A., et al. (1994) Apolipoprotein E associates with β amyloid peptide of Alzheimer’s disease to form novel monofibrils. J. Clin. Invest. 94, 860–869.

    Article  PubMed  CAS  Google Scholar 

  • Saunders A. M., Schmader K., Breitner J. C. S., Benson M. D., Brown W. T., Goldfarb L., et al. (1993) Apolipoprotein E ε4 allele distributions in late-onset Alzheimer’s disease and in other amyloid-forming diseases. Lancet 342, 710–711.

    Article  PubMed  CAS  Google Scholar 

  • Selkoe D. J. (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol. Rev. 81, 741–766.

    PubMed  CAS  Google Scholar 

  • Small D. H. (1998) The amyloid cascade hypothesis debate: emerging consensus on the role of A beta and amyloid in Alzheimer’s disease, in The Sixth International Conference on Alzheimer’s disease, Vol. 5, The Parthenon Publishing Group, Amsterdam, The Netherlands, pp. 301–304.

    Google Scholar 

  • Stine W. B. Jr., Dahlgren K. N., Krafft G. K., and LaDu M. J. (2003) In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis. J. Biol Chem. 278, 11612–11622.

    Article  PubMed  CAS  Google Scholar 

  • Strittmatter W. J., Saunders A. M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G. S., and Roses A. D. (1993) Apolipoprotein E: high avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 1977–1981.

    Article  PubMed  CAS  Google Scholar 

  • Sullivan P. M., Mezdour H., Aratani Y., Knouff C., Najib J., Reddick R. L., et al. (1997) Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J. Biol. Chem. 272, 17972–17980.

    Article  PubMed  CAS  Google Scholar 

  • Terry R. D. 2001 An honorable compromise regarding amyloid in Alzheimer disease. Ann Neurol. 49, 684.

    Article  PubMed  CAS  Google Scholar 

  • Tokuda T., Calero M., Matsubara E., Vidal R., Kumar A., Permanne B., et al. (2000) Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer’s amyloid β-peptide. Biochem. J. 348, 359–365.

    Article  PubMed  CAS  Google Scholar 

  • Tsai M. S., Tangalos E. G., Petersen R. C., Smith G. E., Schaid D. J., Kokmen E., et al. (1994) Apolipoprotein E: risk factor for Alzheimer disease. Am. J. Hum. Genet. 54, 643–649.

    PubMed  CAS  Google Scholar 

  • Urmoneit B., Prikulis I., Wihl G., D’Urso D., Frank R., Heeren J., et al. (1997) Cerebrovascular smooth muscle cells internalize Alzheimer amyloid beta protein via a lipoprotein pathway: implications for cerebral amyloid angiopathy. Lab. Invest. 77, 157–166.

    PubMed  CAS  Google Scholar 

  • van Duijn C. M., de Knijff P., Cruts M., Wehnert A., Havekes L. M., Hofman A., and Van Broeckhoven C. (1994) Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer’s disease. Nat. Genet. 7, 74–78.

    Article  PubMed  Google Scholar 

  • Walsh D. M., Hartley D. M., Kusumoto Y., Fezoui Y., Condron M. M., Lomakin A., et al. (1999) Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J. Biol. Chem. 274, 25945–25952.

    Article  PubMed  CAS  Google Scholar 

  • Walsh D. M., Klyubin I., Fadeeva J. V., Cullen W. K., Anwyl R., Wolfe M. S., et al. (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–539.

    Article  PubMed  CAS  Google Scholar 

  • Whitson J. S., Mims M. P., Strittmatter W. J., Yamaki T., Morrisett J. D., and Appel S. H. (1994) Attenuation of the neurotoxic effect of A beta amyloid peptide by apolipoprotein E. Biochem. Biophys. Res. Commun. 199, 163–170.

    Article  PubMed  CAS  Google Scholar 

  • Winkler K., Scharnagl H., Tisljar U., Hoschutzky H., Friedrich I., Hoffmann M. M., et al. (1999) Competition of Abeta amyloid peptide and apolipoprotein E for receptor-mediated endocytosis. J. Lipid Res. 40, 447–455.

    PubMed  CAS  Google Scholar 

  • Wisniewski T. and Frangione B. (1992) Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci. Lett. 135, 235–238.

    Article  PubMed  CAS  Google Scholar 

  • Wisniewski T., Castano E. M., Golabek A., Vogel T., and Frangione B. (1994) Acceleration of Alzheimer’s fibril formation by apolipoprotein E in vitro. Am. J. Pathol. 145, 1030–1035.

    PubMed  CAS  Google Scholar 

  • Wisniewski T., Golabek A., Matsubara E., Ghiso J., and Frangione B. (1993) Apolipoprotein E: binding to soluble Alzheimer’s beta-amyloid. Biochem. Biophys. Res. Commun. 192, 359–365.

    Article  PubMed  CAS  Google Scholar 

  • Yang D. S., Small D. H., Seydel U., Smith J. D., Hallmayer J., Gandy S. E., and Martins R. N. (1999) Apolipoprotein E promotes the binding and uptake of beta-amyloid into Chinese hamster ovary cells in an isoform-specific manner. Neuroscience 90, 1217–1226.

    Article  PubMed  CAS  Google Scholar 

  • Yang D.- S., Smith J. D., Zhou Z., Gandy S., and Martins R. N. (1997) Characterization of the binding of amyloid-β peptide to cell culture-derived native apolipoprotein E2, E3, and E4 isoforms and to isoforms from human plasma. J. Neurochem. 68, 721–725.

    Article  PubMed  CAS  Google Scholar 

  • Yu C. E., Payami H., Olson J. M., Boehnke M., Wijsman E. M., Orr H. T., et al. (1994) The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease. Am. J. Hum. Genet. 54, 631–642.

    PubMed  CAS  Google Scholar 

  • Zhou Z., Smith J. D., Greengard P., and Gandy S. (1996) Alzheimer amyloid-beta peptide forms denaturant-resistant complex with type epsilon 3 but not type epsilon 4 isoform of native apolipoprotein E. Mol. Med. 2, 175–180.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Geriatrics, Evanston Northwestern Healthcare Research Institute, 60201, Evanston, Illinois

    Arlene M. Manelli, W. Blaine Stine & Mary Jo LaDu

  2. Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL

    Linda J. Van Eldik

  3. Department of Drug Discovery Program, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL

    Linda J. Van Eldik & Mary Jo LaDu

  4. Department of Alzheimer’s Disease Core Center, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL

    Linda J. Van Eldik & Mary Jo LaDu

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  1. Arlene M. Manelli
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  2. W. Blaine Stine
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Correspondence to Mary Jo LaDu.

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Manelli, A.M., Stine, W.B., Van Eldik, L.J. et al. ApoE and Aβ1–42 interactions. J Mol Neurosci 23, 235–246 (2004). https://doi.org/10.1385/JMN:23:3:235

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