Apolipoprotein E: Diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's disease

Journal of Molecular Neuroscience

Volumn 23, Issue 3, 2004, Pages 189-204

  Huang, Yadong ^a   Weisgraber, Karl H ^a   Mucke, Lennart ^a,b   Mahley, Robert W ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Alzheimer's disease; Apolipoprotein E; Proteolysis; Therapeutics; Transgenic mice

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E3; APOLIPOPROTEIN E4; DONEPEZIL; GALANTAMINE; RIVASTIGMINE; TACRINE; TAU PROTEIN; APOLIPOPROTEIN E;

ALZHEIMER DISEASE; AMINO TERMINAL SEQUENCE; ARTICLE; ASTROCYTE; BRAIN NERVE CELL; CARBOXY TERMINAL SEQUENCE; CENTRAL NERVOUS SYSTEM; DRUG TARGETING; EXPERIMENTAL MODEL; GENETIC LINKAGE; HUMAN; LEARNING DISORDER; MEMORY DISORDER; MICROGLIA; NERVE DEGENERATION; NEUROTOXICITY; PATHOPHYSIOLOGY; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN METABOLISM; PROTEIN PHOSPHORYLATION; PROTEIN POLYMORPHISM; PROTEIN STABILITY; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; RISK FACTOR; TRANSGENIC MOUSE; BRAIN; CHEMICAL STRUCTURE; CHEMISTRY; GENETIC VARIABILITY; GENETICS; NERVE CELL; PATHOLOGY; PROTEIN CONFORMATION; REVIEW;

MUS MUSCULUS;

ALZHEIMER DISEASE; APOLIPOPROTEIN E4; APOLIPOPROTEINS E; ASTROCYTES; BRAIN; HUMANS; MODELS, MOLECULAR; NEURONS; PROTEIN CONFORMATION; VARIATION (GENETICS);

EID: 4143091289     PISSN: 08958696     EISSN: None     Source Type: Journal    
DOI: 10.1385/JMN:23:3:189     Document Type: Article

References (157)

1. Aggerbeck L. P., Wetterau J. R., Weisgraber K. H., Wu C.-S. C., and Lindgren F. T. (1988) Human apolipoprotein E3 in aqueous solution. II. Properties of the amino- and carboxyl-terminal domains. J. Biol. Chem. 263, 6249-6258.
2. Aoki K., Uchihara T., Sanjo N., Nakamura A., Ikeda K., Tsuchiya K., et al. (2003) Increased expression of neuronal apolipoprotein E in human brain with cerebral infarction. Stroke 34, 875-880.
3. V717F transgenic mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 96, 15233-15238.
4. Bao F., Arai H., Matsushita S., Higuchi S., and Sasaki H. (1996) Expression of apolipoprotein E in normal and diverse neurodegenerative disease brain. Neuroreport 7, 1733-1739.
5. Basu S. K., Brown M. S., Ho Y. K., Havel R. J., and Goldstein J. L. (1981) Mouse macrophages synthesize and secrete a protein resembling apolipoprotein E. Proc. Natl. Acad. Sci. USA 78, 7545-7549.
6. Beffert U. and Poirier J. (1996) Apolipoprotein E, plaques, tangles and cholinergic dysfunction in Alzheimer's disease. Ann. N. Y. Acad. Sci. 777, 166-174.
7. Bellosta S., Nathan B. P., Orth M., Dong L.-M., Mahley R. W., and Pitas R. E. (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.
8. Biernat J., Mandelkow E.- M., Schröter C., Lichtenberg-Kraag B., Steiner B., Berling B., et al. (1992) The switch of tau protein to an Alzheimer-like state includes the phosphorylation of two serine-proline motifs upstream of the microtubule binding region. EMBO J. 11, 1593-1597.
9. Boschert U., Merlo-Pich E., Higgins G., Roses A. D., and Catsicas S. (1999) Apolipoprotein E expression by neurons surviving excitotoxic stress. Neurobiol. Dis. 6, 508-514.
10. Boyles J. K., Pitas R. E., Wilson E., Mahley R. W., and Taylor J. M. (1985) Apolipoprotein E associated with astrocytic glia of the central nervous system and with non-myelinating glia of the peripheral nervous system. J. Clin. Invest. 76, 1501-1513.
11. Boyles J. K., Zoellner C. D., Anderson L. J., Kosik L. M., Pitas R. E., Weisgraber K. H., et al. (1989) A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J. Clin. Invest. 83, 1015-1031.
12. Brecht W. J., Harris F. M., Chang S., Tesseur I., Liu G.-Q., Xu, Q., et al. (2004) Neuron-specific apolipoprotein E4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J. Neurosci. 24, 2527-2534.
13. Buttini M., Akeefe H., Lin C., Mahley R. W., Pitas R. E., Wyss-Coray T., et al. (2000) Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease. Neuroscience 97, 207-210.
14. -/- mice: isoform-specific effects on neurodegeneration. J. Neurosci. 19, 4867-4880.
15. Buttini M., Yu G.-Q., Shockley K., Huang Y., Jones B., Masliah E., et al. (2002) Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid β peptides but not on plaque formation. J. Neurosci. 22, 10539-10548.
16. Cedazo-Mínguez A., Hamker U., Meske V., Veh R. W., Hellweg R., Jacobi C., et al. (2001) Regulation of apolipoprotein E secretion in rat primary hippocampal astrocyte cultures. Neuroscience 105, 651-661.
17. Cho H. S., Hyman B. T., Greenberg S. M., and Rebeck G. W. (2001) Quantisation of apoE domains in Alzheimer disease brain suggests a role for apoE in Aβ aggregation. J. Neuropathol. Exp. Neurol. 60, 342-349.
18. Corder E. H., Saunders A. 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.
19. Dekroon R. M. and Armati P. J. (2001) Synthesis and processing of apolipoprotein E in human brain cultures. Glia 33, 298-305.
20. DeMattos R. B., Curtiss L. K., and Williams D. L. (1998) A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins. J. Biol. Chem. 273, 4206-4212.
21. DeMattos R. B., Rudel L. L., and Williams D. L. (2001) Biochemical analysis of cell-derived apoE3 particles active in stimulating neurite outgrowth. J. Lipid Res. 42, 976-987.
22. Diedrich J. F., Minnigan H., Carp R. I., Whitaker J. N., Race R., Frey W. II, and Haase A. T. (1991) Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes. J. Virol. 65, 4759-4768.
23. Dong L.-M. and Weisgraber K. H. (1996) Human apolipoprotein E4 domain interaction. Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins. J. Biol. Chem. 271, 19053-19057.
24. Dong L.-M., Wilson C., Wardell M. R., Simmons T., Mahley R. W., Weisgraber K. H., et al. (1994) Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms. J. Biol. Chem. 269, 22358-22365.
25. Drouet B., Fifre A., Pinçon-Raymond M., Vandekerckhove J., Rosseneu M., Guéant J.- L., et al. (2001) ApoE protects cortical neurones against neuro- toxicity induced by the non-fibrillar C-terminal domain of the amyloid-β peptide. J. Neurochem. 76, 117-127.
26. Dupont-Wallois L., Soulié C., Sergeant N., Wavrant-de Wrieze N., Chartier-Harlin M.- C., et al. (1997) ApoE synthesis in human neuroblastoma cells. Neurobiol. Dis. 4, 356-364.
27. Elshourbagy N. A., Liao W. S., Mahley R. W., and Taylor J. M. (1985) Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc. Natl. Acad. Sci. USA 82, 203-207.
28. Estus S., Tucker H. M., van Rooyen C., Wright S., Brigham E. F., Wogulis M., et al. (1997) Aggregated amyloid-β protein induces cortical neuronal apoptosis and concomitant "apoptotic" pattern of gene induction. J. Neurosci. 17, 7736-7745.
29. Fagan A. M., Bu G., Sun Y., Daugherty A., and Holtzman D. M. (1996) Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein. J. Biol. Chem. 271, 30121-30125.
30. Fagan A. M., Holtzman D. M., Munson G., Mathur T., Schneider D., Chang L. K., et al. (1999) Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-), and human apoE transgenic mice. J. Biol. Chem. 274, 30001-30007.
31. Farrer L. A., Cupples L. A., Haines J. L., Hyman B., Kukull W. A., Mayeux R., et al. (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA 278, 1349-1356.
32. Ferreira S., Dupire M.-J., Delacourte A., Najib J., and Caillet-Boudin M.-L. (2000) Synthesis and regulation of apolipoprotein E during the differentiation of human neuronal precursor NT2/D1 cells into postmitotic neurons. Exp. Neurol. 166, 415-421.
33. Friedhoff P., von Bergen M., Mandelkow E.-M., and Mandelkow E. (2000) Structure of tau protein and assembly into paired helical filaments. Biochim. Biophys. Acta 1502, 122-132.
34. Goedert M., Spillantini M. G., Cairns N. J., and Crowther R. A. (1992) Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8, 159-168.
35. Gong J.- S., Kobayashi M., Hayashi H., Zou K., Sawamura N., Fujita S. C., et al. (2002) Apolipoprotein E (apoE) isoform-dependent lipid release from astrocytes prepared from human apoE3 and apoE4 knock-in mice. J. Biol. Chem. 277, 29919-29926.
36. 4 in humans. J. Clin. Invest. 78, 815-821.
37. Grehan S., Allan C., Tse E., Walker D., and Taylor J. M. (200Ia) Expression of the apolipoprotein E gene in the skin is controlled by a unique downstream enhancer. J. Invest. Dermatol. 116, 77-84.
38. Grehan S., Tse E., and Taylor J. M. (2001b) Two distal downstream enhancers direct expression of the human apolipoprotein E gene to astrocytes in the brain. J. Neurosci. 21, 812-822.
39. Han S.-H., Einstein G., Weisgraber K. H., Strittmatter W. J., Saunders A. M., Pericak-Vance M., et al. (1994) Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study. J. Neuropathol. Exp. Neurol. 53, 535-544.
40. Handelmann G. E., Boyles J. K., Weisgraber K. H., Mahley R. W., and Pitas R. E. (1992) Effects of apolipoprotein E, β-very low density lipoproteins, and cholesterol on the extension of neurites by rabbit dorsal root ganglion neurons in vitro. J. Lipid Res. 33, 1677-1688.
41. 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.
42. Harris F. M., Brecht W. J., Xu Q., Tesseur I., Kekonius L., Wyss-Coray T., et al. (2003) Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer disease-like neurodegeneration and behavioral deficits in transgenic mice. Proc. Natl. Acad. Sci. USA 100, 10966-10971.
43. Harris F. M., Tesseur I., Brecht W. J., Xu Q., Mullendorf K., Chang S., et al. (2004) Astroglial regulation of apolipoprotein E expression in neuronal cells. Implications for Alzheimer's disease. J. Biol. Chem. 279, 3862-3868.
44. Hartman R. E., Wozniak D. F., Nardi A., Olney J. W., Sartorius L., and Holtzman D. M. (2001) Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology. Exp. Neurol. 170, 326-344.
45. Hebert L. E., Scherr P. A., Bienias J. L., Bennett D. A., and Evans D. A. (2003) Alzheimer disease in the US population. Prevalence estimates using the 2000 census. Arch. Neurol. 60, 1119-1122.
46. Herz J. and Beffert U. (2000) Apolipoprotein E receptors: linking brain development and Alzheimer's disease. Nat. Rev. Neurosci. 1, 51-58.
47. Holtzman D. M., Bales K. R., Tenkova T., Fagan A. M., Parsadanian M., Sartorius L. J., et al. (2000a) 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.
48. Holtzman D. M., Fagan A. M., Mackey B., Tenkova T., Sartorius L., Paul S. M., et al. (2000b) Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model. Ann. Neurol. 47, 739-747.
49. Holtzman D. M., Pitas R. E., Kilbridge J., Nathan B., Mahley R. W., Bu G., et al. (1995) Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line. Proc. Natl. Acad. Sci. USA 92, 9480-9484.
50. Huang Y. and Mahley R. W. (1999) Apolipoprotein E and human disease, in Plasma Lipids and Their Role in Disease, Barter, P. J., and Rye, K.-A., eds., Harwood Academic Publishers, Amsterdam, The Netherlands, pp. 257-284.
51. Huang Y., Liu X. Q., Wyss-Coray T., Brecht W. J., Sanan D. A., and Mahley R. W. (2001) Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons. Proc. Natl. Acad. Sci. USA 98, 8838-8843.
52. Ignatius M. J., Gebicke-Härter P. J., Skene J. H. P., Schilling J. W., Weisgraber K. H., Mahley R. W., et al. (1986) Expression of apolipoprotein E during nerve degeneration and regeneration. Proc. Natl. Acad. Sci. USA 83, 1125-1129.
53. Ignatius M. J., Shooter E. M., Pitas R. E., and Mahley R. W. (1987) Lipoprotein uptake by neuronal growth cones in vitro. Science 236, 959-962.
54. Innerarity T. L., Mahley R. W., Weisgraber K. H., and Bersot T. P. (1978) Apoprotein (E-A-II) complex of human plasma lipoproteins. II. Receptor binding activity of a high density lipoprotein subfraction modulated by the apo(E-A-II) complex. J. Biol. Chem. 253, 6289-6295.
55. V717F transgenic mice. Acta Neuropathol. 100, 451-458.
56. Jacobsen J. S. (2002) Alzheimer's disease: an overview of current and emerging therapeutic strategies. Curr. Top. Med. Chem. 2, 343-352.
57. Ji Y., Permanne B., Sigurdsson E. M., Holtzman D. M., and Wisniewski T. (2001) Amyloid β40/42 clearance across the blood-brain barrier following intra-ventricular injections in wild-type, apoE knock-out and human apoE3 or E4 expressing transgenic mice. J. Alzheimers Dis. 3, 23-30.
58. Ji Z.-S., Miranda R. D., Newhouse Y. M., Weisgraber K. H., Huang Y., and Mahley R. W. (2002) Apolipoprotein E4 potentiates amyloid β peptide-induced lysosomal leakage and apoptosis in neuronal cells. J. Biol. Chem. 277, 21821-21828.
59. Jordan 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.
60. 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, 23403-23406.
61. 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, 9039-9042.
62. Lauderback C. M., Kanski J., Hackett J. M., Maeda N., Kindy M. S., and Butterfield D. A. (2002) Apolipoprotein E modulates Alzheimer's Aβ(1-42)-induced oxidative damage to synaptosomes in an allele-specific manner. Brain Res. 924, 90-97.
63. LeBlanc A. C. and Poduslo J. F. (1990) Regulation of apolipoprotein E gene expression after injury of the rat sciatic nerve. J. Neurosci. Res. 25, 162-171.
64. LeBlanc A., Liu H., Goodyer C., Bergeron C., and Hammond J. (1999) Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease. J. Biol. Chem. 274, 23426-23436.
65. Lesuisse C., Xu G., Anderson J., Wong M., Jankowsky J., Holtz G., et al. (2001) Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice. Hum. Mol. Genet. 10, 2525-2537.
66. Lewis J., McGowan E., Rockwood J., Melrose H., Nacharaju P., Slegtenhorst M. V., et al. (2000) Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 25, 402-405.
67. Ljungberg M. C., Dayanandan R., Asuni A., Rupniak T. H., Anderton B. H., and Lovestone S. (2002) Truncated apoE forms tangle-like structures in a neuronal cell line. Neuroreport 13, 867-870.
68. Loo D. T., Copani A., Pike C. J., Whittemore E. R., Walencewicz A. J., and Cotman C. W. (1993) Apoptosis is induced by β-amyloid in cultured central nervous system neurons. Proc. Natl. Acad. Sci. USA 90, 7951-7955.
69. Lovestone S., Anderton B. H., Hartley K., Jensen T. G., and Jorgensen A. L. (1996) The intracellular fate of apolipoprotein E is tau dependent and apoe allele-specific. Neuroreport 7, 1005-1008.
70. 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments. Nature 372, 92-94.
71. Mahley R. W. (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240, 622-630.
72. Mahley R. W. and Huang Y. (1999) Apolipoprotein E: from atherosclerosis to Alzheimer's disease and beyond. Curr. Opin. Lipidol. 10, 207-217.
73. Mahley R. and Huang Y. (2003) Apolipoprotein E: structure and function in lipid metabolism and neurobiology, in The Molecular and Genetic Basis of Neurologic and Psychiatric Disease, 3rd ed., Rosenberg, R. N., Prusiner, S. B., DiMauro, S., Barchi, R. L., and Nestler, E. J., eds., Butterworth Heinemann, Philadelphia, PA, pp. 565-573.
74. Mahley R. W. and Rall S. C., Jr. (2000) Apolipoprotein E: far more than a lipid transport protein. Annu. Rev. Genomics Hum. Genet. 1, 507-537.
75. Mahley R. W., Nathan B. P., Bellosta S., and Pitas R. E. (1995) Apolipoprotein E: impact of cytoskeletal stability in neurons and the relationship to Alzheimer's disease. Curr. Opin. Lipidol. 6, 86-91.
76. Marques M. A., Tolar M., Harmony J. A. K., and Crutcher K. A. (1996) A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity. Neuroreport 7, 2529-2532.
77. Martel C. L., Mackic J. B., Matsubara E., Governale S., Miguel C., Miao W., et al. (1997) Isoform-specific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer's amyloid β. J. Neurochem. 69, 1995-2004.
78. Masliah E., Mallory M., Ge N., Alford M., Veinbergs I., and Roses A. D. (1995) Neurodegeneration in the central nervous system of apoE-deficient mice. Exp. Neurol. 136, 107-122.
79. Mazur-Kolecka B., Frackowiak J., Kowal D., Krzeslowska J., and Dickson D. (2002) Oxidative protein damage in cells engaged in β-amyloidosis is related to apoE genotype. Neuroreport 13, 465-468.
80. Messmer-Joudrier S., Sagot Y., Mattenberger L., James R. W., and Kato A. C. (1996) Injury-induced synthesis and release of apolipoprotein E and clusterin from rat neural cells. Eur. J. Neurosci. 8, 2652-2661.
81. Metzger R. E., LaDu M. J., Pan J. B., Getz G. S., Frail D. E., and Falduto M. T. (1996) Neurons of the human frontal cortex display apolipoprotein E immunoreactivity: implications for Alzheimer's disease. J. Neuropathol. Exp. Neurol. 55, 372-380.
82. Miyata M. and Smith J. D. (1996) Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and β-amyloid peptides. Nat. Genet. 14, 55-61.
83. Moir R. D., Atwood C. S., Romano D. M., Laurans M. H., Huang X., Bush A. I., et al. (1999) Differential effects of apolipoprotein E isoforms on metal-induced aggregation of Aβ using physiological concentrations. Biochemistry 38, 4595-4603.
84. Morishima Y., Gotoh Y., Zieg J., Barrett T., Takano H., Flavell R., et al. (2001) β-Amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J. Neurosci. 21, 7551-7560.
85. Morrow J. A., Hatters D. M., Lu B., Höchtl P., Oberg K. A., Rupp B., et al. (2002) Apolipoprotein E4 forms a molten globule: a potential basis for its association with disease. J. Biol. Chem. 277, 50380-50385.
86. Morrow J. A., Segall M. L., Lund-Katz S., Phillips M. C., Knapp M., Rupp B., et al. (2000) Differences in stability among the human apolipoprotein E isoforms determined by the amino-terminal domain. Biochemistry 39, 11657-11666.
87. Mulder M., Blokland A., van den Berg D.-J., Schulten H., Bakker A. H. F., Terwel D., et al. (2001) Apolipoprotein E protects against neuropathology induced by a high-fat diet and maintains the integrity of the blood-brain barrier during aging. Lab. Invest. 81, 953-960.
88. Müller H. W., Gebicke-Härter P. J., Hangen D. H., and Shooter E. M. (1985) A specific 37,000-dalton protein that accumulates in regenerating but not in nonregenerating mammalian nerves. Science 228, 499-501.
89. Müller H. W., Ignatius M. J., Hangen D. H., and Shooter E. M. (1986) Expression of specific sheath cell proteins during peripheral nerve growth and regeneration in mammals. J. Cell Biol. 102, 393-402.
90. Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B. A., and Yuan J. (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 403, 98-103.
91. 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 and kuru plaque amyloid in Creutzfeldt-Jakob disease. Brain Res. 541, 163-166.
92. Nathan B. P., Bellosta S., Sanan D. A., Weisgraber K. H., Mahley R. W., and Pitas R. E. (1994) Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science 264, 850-852.
93. Nathan B. P., Chang K.-C., Bellosta S., Brisch E., Ge N., Mahley R. W., et al. (1995a) The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated with microtubule depolymerization. J. Biol. Chem. 270, 19791-19799.
94. Nathan B. P., Chang K.- C., Bellosta S., Mahley R. W., and Pitas R. E. (1995b) The inhibition of neurite outgrowth by apolipoprotein E4 is mediated through the low density lipoprotein receptor-related protein. Soc. Neurosci. 21(Part 2), 1009 (abstract).
95. Nicoll J. A. R., Roberts G. W., and Graham D. I. (1996) Amyloid β-protein, APOE genotype and head injury. Ann. N. Y. Acad. Sci. 777, 271-275.
96. Pasinetti G. M., Hassler M., Stone D., and Finch C. E. (1999) Glial gene expression during aging in rat striatum and in long-term responses to 6-OHDA lesions. Synapse 31, 278-284.
97. Pastor P., Roe C. M., Villegas A., Bedoya G., Chakraverty S., García G., et al. (2003) Apolipoprotein Eε4 modifies Alzheimer's disease onset in an E280A PS1 kindred. Ann. Neurol. 54, 163-169.
98. Pillot T., Goethals M., Najib J., Labeur C., Lins L., Chambaz J., et al. (1999) β-Amyloid peptide interacts specifically with the carboxy-terminal domain of human apolipoprotein E: relevance to Alzheimer's disease. J. Neurochem. 72, 230-237.
99. Pitas R. E., Boyles J. K., Lee S. H., Foss D., and Mahley R. W. (1987a) Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochim. Biophys. Acta 917, 148-161.
100. Pitas R. E., Boyles J. K., Lee S. H., Hui D., and Weisgraber K. H. (1987b) Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J. Biol. Chem. 262, 14352-14360.
101. Poirier J., Delisle M.-C., Quirion R., Aubert I., Farlow M., Lahiri D., et al. (1995) Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc. Natl. Acad. Sci. USA 92, 12260-12264.
102. Poirier J., Hess M., May P. C., and Finch C. E. (1991) Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning. Mol. Brain Res. 11, 97-106.
103. Raber J., Bongers G., LeFevour A., Buttini M., and Mucke L. (2002) Androgens protect against apolipoprotein E4-induced cognitive deficits. J. Neurosci. 22, 5204-5209.
104. Raber J., Wong D., Buttini M., Orth M., Bellosta S., Pitas R. E., et al. (1998) Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females. Proc. Natl. Acad. Sci. USA 95, 10914-10919.
105. Raber J., Wong D., Yu G.-Q., Buttini M., Mahley R. W., Pitas R. E., et al. (2000) Apolipoprotein E and cognitive performance. Nature 404, 352-354.
106. Raffaï R. L., Dong L.-M., Farese R. V., Jr., and Weisgraber K. H. (2001) Introduction of human apolipoprotein E4 "domain interaction" into mouse apolipoprotein E. Proc. Natl. Acad. Sci. USA 98, 11587-11591.
107. Rall S. C., Jr., Weisgraber K. H., Innerarity T. L., and Mahley R. W. (1982a) Structural basis for receptor binding heterogeneity of apolipoprotein E from type III hyperlipoproteinemic subjects. Proc. Natl. Acad. Sci. USA 79, 4696-4700.
108. Rall S. C., Jr., Weisgraber K. H., and Mahley R. W. (1982b) Human apolipoprotein E. The complete amino acid sequence. J. Biol. Chem. 257, 4171-4178.
109. Rapoport M., Dawson H. N., Binder L. I., Vitek M. P., and Ferreira A. (2002) Tau is essential to β-amyloid-induced neurotoxicity. Proc. Natl. Acad. Sci. USA 99, 6364-6369.
110. Romas S. N., Santana V., Williamson J., Ciappa A., Lee J. H., Rondon H. Z., et al. (2002) Familial Alzheimer disease among Caribbean Hispanics. A reexamination of its association with APOE. Arch. Neurol. 59, 87-91.
111. Roses A. D. (1996) Apolipoprotein E alleles as risk factors in Alzheimer's disease. Annu. Rev. Med. 47, 387-400.
112. Sanan D. A., Weisgraber K. H., Russell 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. Isoform apoE4 associates more efficiently than apoE3. J. Clin. Invest. 94, 860-869.
113. Saunders A. M., Strittmatter W. J., Schmechel D., St George-Hyslop P. H., Pericak-Vance M. A., Joo S. H., et al. (1993) Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43, 1467-1472.
114. Saura J., Petegnief V., Wu X., Liang Y., and Paul S. M. (2003) Microglial apolipoprotein E and astroglial apolipoprotein J expression in vitro: opposite effects of lipopolysaccharide. J. Neurochem. 85, 1455-1467.
115. Schneider A., Biernat J., von Bergen M., Mandelkow E., and Mandelkow E.-M. (1999) Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry 38, 3549-3558.
116. Selkoe D. J. (2001) Clearing the brain's amyloid cobwebs. Neuron 32, 177-180.
117. 1-40 peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J. Clin. Invest. 106, 1489-1499.
118. Shih S.-J., Allan C., Grehan S., Tse E., Moran C., and Taylor J. M. (2000) Duplicated downstream enhancers control expression of the human apolipoprotein E gene in macrophages and adipose tissue. J. Biol. Chem. 275, 31567-31572.
119. Skene J. H. P. and Shooter E. M. (1983) Denervated sheath cells secrete a new protein after nerve injury. Proc. Natl. Acad. Sci. USA 80, 4169-4173.
120. Soulié C., Mitchell V., Dupont-Wallois L., Chartier-Harlin M.-C., Beauvillain J.-C., Delacourte A., et al. (1999) Synthesis of apolipoprotein E (apoE) mRNA by human neuronal-type SK N SH-SY 5Y cells and its regulation by nerve growth factor and apoE. Neurosci. Lett. 265, 147-150.
121. Steinmetz A., Jakobs C., Motzny S., and Kaffarnik H. (1989) Differential distribution of apolipoprotein E isoforms in human plasma lipoproteins. Arteriosclerosis 9, 405-411.
122. Strittmatter W. J., Saunders A. M., Goedert M., Weisgraber K. H., Dong L.-M., Jakes R., et al. (1994a) Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease. Proc. Natl. Acad. Sci. USA 91, 11183-11186.
123. Strittmatter W. J., Saunders A. M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G. S., et. al. (1993a) 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.
124. Strittmatter W. J., Weisgraber K. H., Goedert M., Saunders A. M., Huang D., Corder E. H., et al. (1994b) Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Exp. Neurol. 125, 163-171.
125. Strittmatter W. J., Weisgraber K. H., Huang D. Y., Dong L.-M., Salvesen G. S., Pericak-Vance M., et al. (1993b) Binding of human apolipoprotein E to synthetic amyloid β peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 8098-8102.
126. Sun Y., Wu S., Bu G., Onifade M. K., Patel S. N., LaDu M. J., et al. (1998) Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins. J. Neurosci. 18, 3261-3272.
127. Tang M.-X., Stern Y., Marder K., Bell K., Gurland B., Lantigua R., et al. (1998) The APOE-ε4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA 279, 751-755.
128. Tesseur I., Van Dorpe J., Bruynseels K., Bronfman F., Sciot R., Van Lommel A., et al. (2000b) Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord. Am. J. Pathol. 157, 1495-1510.
129. Tesseur I., Van Dorpe J., Spittaels K., Van den Haute C., Moechars D., and Van Leuven F. (2000a) Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice. Am. J. Pathol. 156, 951-964.
130. Tolar M., Keller J. N., Chan S., Mattson M. P., Marques M. A., and Crutcher K. A. (1999) Truncated apolipoprotein E (apoE) causes increased intracellular calcium and may mediate apoE neurotoxicity. J. Neurosci. 19, 7100-7110.
131. Tolar M., Marques M. A., Harmony J. A. K., and Crutcher K. A. (1997) Neurotoxicity of the 22 kDa thrombin-cleavage fragment of apolipoprotein E and related synthetic peptides is receptor-mediated. J. Neurosci. 17, 5678-5686.
132. Troy C. M., Rabacchi S. A., Friedman W. J., Frappier T. F., Brown K., and Shelanski M. L. (2000) Caspase-2 mediates neuronal cell death induced by β-amyloid. J. Neurosci. 20, 1386-1392.
133. Troy C. M., Rabacchi S. A., Xu Z., Maroney A. C., Connors T. J., Shelanski M. L., et al. (2001) β-Amyloid-induced neuronal apoptosis requires c-JunN-terminal kinase activation. J. Neurochem. 77, 157-164.
134. Uetsuki T., Takemoto K., Nishimura I., Okamoto M., Niinobe M., Momoi T., et al. (1999) Activation of neuronal caspase-3 by intracellular accumulation of wild-type Alzheimer amyloid precursor protein. J. Neurosci. 19, 6955-6964.
135. Utermann G., Langenbeck U., Beisiegel U., and Weber W. (1980) Genetics of the apolipoprotein E system in man. Am. J. Hum. Genet. 32, 339-347.
136. Utermann G., Steinmetz A., and Weber W. (1982) Genetic control of human apolipoprotein E polymorphism: comparison of one- and two-dimensional techniques of isoprotein analysis. Hum. Genet. 60, 344-351.
137. Vincent B. and Smith J. D. (2001) Astrocytes down-regulate neuronal β-amyloid precursor protein expression and modify its processing in an apolipoprotein E isoform-specific manner. Eur. J. Neurosci. 14, 256-266.
138. Weisgraber K. H. (1990) Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112. J. Lipid Res. 31, 1503-1511.
139. Weisgraber K. H. (1994) Apolipoprotein E: structure-function relationships. Adv. Protein Chem. 45, 249-302.
140. Weisgraber K. H. and Mahley R. W. (1978) Apoprotein (E-A-II) complex of human plasma lipoproteins. I. Characterization of this mixed disulfide and its identification in a high density lipoprotein subfraction. J. Biol. Chem. 253, 6281-6288.
141. Weisgraber K. H. and Mahley R. W. (1996) Human apolipoprotein E: the Alzheimer's disease connection. FASEB J. 10, 1485-1494.
142. Weisgraber K. H. and Shinto L. H. (1991) Identification of the disulfide-linked homodimer of apolipoprotein E3 in plasma. Impact on receptor binding activity. J. Biol. Chem. 266, 12029-12034.
143. Weisgraber K. H., Pitas R. E., and Mahley R. W. (1994a) Lipoproteins, neurobiology, and Alzheimer's disease: structure and function of apolipoprotein E. Curr. Opin. Struct. Biol. 4, 507-515.
144. Weisgraber K. H., Rall S. C., Jr., and Mahley R. W. (1981) Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J. Biol. Chem. 256, 9077-9083.
145. Weisgraber K. H., Roses A. D., and Strittmatter W. J. (1994b) The role of apolipoprotein E in the nervous system. Curr. Opin. Lipidol. 5, 110-116.
146. Werb Z. and Chin J. R. (1983) Onset of apoprotein E secretion during differentiation of mouse bone marrow-derived mononuclear phagocytes. J. Cell Biol. 97, 1113-1118.
147. Wetterau J. R., Aggerbeck L. P., Rall S. C., Jr., and Weisgraber K. H. (1988) Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains. J. Biol. Chem. 263, 6240-6248.
148. Wilson C., Wardell M. R., Weisgraber K. H., Mahley R. W., and Agard D. A. (1991) Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E. Science 252, 1817-1822.
149. Wisniewski T. and Frangione B. (1992) Apolipoprotein E: a pathological
150. Wisniewski T., Castaño 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.
151. Xu P.-T., Gilbert J. R., Qiu H.-L., Ervin J., Rothrock-Christian T. R., Hulette C., et al. (1999a) Specific regional transcription of apolipoprotein E in human brain neurons. Am. J. Pathol. 154, 601-611.
152. Xu P.-T., Gilbert J. R., Qiu H.-L., Rothrock-Christian T., Settles D. L., Roses A. D., et al. (1998) Regionally specific neuronal expression of human APOE gene in transgenic mice. Neurosci. Lett. 246, 65-68.
153. s) is preferentially associated with neuron-enriched cultures from APOE transgenic mice. Neurobiol. Dis. 6, 63-75.
154. Xu, P.-T., Schmechel D., Rothrock-Christian T., Burkhart D. S., Qiu H.-L., Popko B., et al. (1996) Human apolipoprotein E2, E3, and E4 isoform-specific transgenic mice: human-like pattern of glial and neuronal immunoreactivity in central nervous system not observed in wild-type mice. Neurobiol. Dis. 3, 229-245.
155. Yankner B. A., Dawes L. R., Fisher S., Villa-Komaroff L., Oster-Granite M. L., and Neve R. L. (1989) Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science 245, 417-420.
156. Zannis V. I. and Breslow J. L. (1981) Human very lowdensity lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification. Biochemistry 20, 1033-1041.
157. Zannis V. I., Just P. W., and Breslow J. L. (1981) Human apolipoprotein E isoprotein subclasses are genetically determined. Am. J. Hum. Genet. 33, 11-24.