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Cited by 320Alzheimer's disease research and treatmentsCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

Apolipoprotein E: From lipid transport to neurobiology

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Hauser, Paul S., Narayanaswami, Vasanthy, Ryan, Robert O.·2011·Progress in Lipid Research
DOI 10.1016/j.plipres.2010.09.001PMC PMC3022415
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Abstract

Apolipoprotein (apo) E has a storied history as a lipid transport protein. The integral association between cholesterol homeostasis and lipoprotein clearance from circulation are intimately related to apoE's function as a ligand for cell-surface receptors of the low-density lipoprotein receptor family. The receptor binding properties of apoE are strongly influenced by isoform specific amino acid differences as well as the lipidation state of the protein. As understanding of apoE as a structural component of circulating plasma lipoproteins has evolved, exciting developments in neurobiology have revitalized interest in apoE. The strong and enduring correlation between the apoE4 isoform and age of onset and increased risk of Alzheimer's disease has catapulted apoE to the forefront of neurobiology. Using genetic tools generated for study of apoE lipoprotein metabolism, transgenic "knock-in" and gene-disrupted mice are now favored models for study of its role in a variety of neurodegenerative diseases. Key structural knowledge of apoE and isoform-specific differences is driving research activity designed to elucidate how a single amino acid change can manifest such profoundly significant pathological consequences. This review describes apoE through a lens of structure-based knowledge that leads to hypotheses that attempt to explain the functions of apoE and isoform-specific effects relating to disease mechanism.

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  • Binding of lipids is required for ApoE to acquire a biologically active conformation necessary for recognition and binding to members of the LDLR family and its internalization.

    “The binding of lipids is required for ApoE to acquire a biologically active conformation, which is necessary for recognition and binding to the members of the low-density lipoprotein receptor (LDLR) family and its internalization (24).”

    From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [24]

  • Studies of brain histology, neurodegenerative markers, cholinergic activity, and neuronal function in knockout mice have been equivocal.

    “Studies of brain histology, neurodegenerative markers, cholinergic activity, and neuronal function in knockout mice have been equivocal.39”

    From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [39]

  • Apolipoprotein E is produced and secreted mainly by astrocytes and is believed to be important for normal brain function.

    “Produced and secreted mainly by astrocytes,39 it is believed to be important for normal brain function.”

    From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [39]

  • ApoE is a lipid-binding protein that transports lipids across organs in the periphery and between different cell types in the brain.

    “Apolipoprotein E (ApoE) is a lipid-binding protein that transports lipids across organs in the periphery and between different cell types in the brain (Hauser et al., 2011).”

    From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Hauser et al., 2011

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References 252 · Cited by 320

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  1. [1]Shimano H Yamada N Katsuki M Shimada M Gotoda T Harada K Overexpression of apolipoprotein E in transgenic mice: marked reduction in plasma lipoproteins except high density lipoprotein and resistance against diet-induced hypercholesterolemia Proceedings of the National Academy of Sciences of the United States of America 1992 89 1750 4 1542669 PMC48530
  2. [2]Shimano H Ohsuga J Shimada M Namba Y Gotoda T Harada K Inhibition of diet-induced atheroma formation in transgenic mice expressing apolipoprotein E in the arterial wall The Journal of clinical investigation 1995 95 469 76 7860728 PMC295491
  3. [3]Zhang SH Reddick RL Piedrahita JA Maeda N Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E Science (New York, NY 1992 258 468 71 1411543
  4. [4]Ghiselli G Schaefer EJ Gascon P Breser HB Jr Type III hyperlipoproteinemia associated with apolipoprotein E deficiency Science (New York, NY 1981 214 1239 41 6795720
  5. [5]Zannis VI McPherson J Goldberger G Karathanasis SK Breslow JL Synthesis, intracellular processing, and signal peptide of human apolipoprotein E The Journal of biological chemistry 1984 259 5495 9 6325438
  6. [7]McLean JW Elshourbagy NA Chang DJ Mahley RW Taylor JM Human apolipoprotein E mRNA. cDNA cloning and nucleotide sequencing of a new variant The Journal of biological chemistry 1984 259 6498 504 6327682
  7. [8]Olaisen B Teisberg P Gedde-Dahl T Jr The locus for apolipoprotein E (apoE) is linked to the complement component C3 (C3) locus on chromosome 19 in man Hum Genet 1982 62 233 6 7169215
  8. [9]Paik YK Chang DJ Reardon CA Davies GE Mahley RW Taylor JM Nucleotide sequence and structure of the human apolipoprotein E gene Proceedings of the National Academy of Sciences of the United States of America 1985 82 3445 9 2987927 PMC397792
  9. [10]Bellosta S Mahley RW Sanan DA Murata J Newland DL Taylor JM Macrophage-specific expression of human apolipoprotein E reduces atherosclerosis in hypercholesterolemic apolipoprotein E-null mice The Journal of clinical investigation 1995 96 2170 9 7593602 PMC185866
  10. [11]Mazzone T Apolipoprotein E secretion by macrophages: its potential physiological functions Curr Opin Lipidol 1996 7 303 7 8937521
  11. [12]Tangirala RK Pratico D FitzGerald GA Chun S Tsukamoto K Maugeais C Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E The Journal of biological chemistry 2001 276 261 6 11024044
  12. [13]Mahley RW Apolipoprotein E: cholesterol transport protein with expanding role in cell biology Science (New York, NY 1988 240 622 30 3283935
  13. [15]Segrest JP Jones MK De Loof H Brouillette CG Venkatachalapathi YV Anantharamaiah GM The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function J Lipid Res 1992 33 141 66 1569369
  14. [16]Chou PY Fasman GD Prediction of protein conformation Biochemistry 1974 13 222 45 4358940
  15. [17]Chou PY Fasman GD Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins Biochemistry 1974 13 211 22 4358939
  16. [19]De Pauw M Vanloo B Weisgraber K Rosseneu M Comparison of lipid-binding and lecithin:cholesterol acyltransferase activation of the amino- and carboxyl-terminal domains of human apolipoprotein E3 Biochemistry 1995 34 10953 66 7662677
  17. [20]Wetterau JR Aggerbeck LP Rall SC Jr Weisgraber KH Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains The Journal of biological chemistry 1988 263 6240 8 3360781
  18. [21]Sakamoto T Tanaka M Vedhachalam C Nickel M Nguyen D Dhanasekaran P Contributions of the carboxyl-terminal helical segment to the self-association and lipoprotein preferences of human apolipoprotein E3 and E4 isoforms Biochemistry 2008 47 2968 77 18201068 PMC2692928
  19. [23]Yokoyama S Kawai Y Tajima S Yamamoto A Behavior of human apolipoprotein E in aqueous solutions and at interfaces The Journal of biological chemistry 1985 260 16375 82 4066713
  20. [24]Fan D Li Q Korando L Jerome WG Wang J A monomeric human apolipoprotein E carboxyl-terminal domain Biochemistry 2004 43 5055 64 15109264
  21. [26]Utermann G Langenbeck U Beisiegel U Weber W Genetics of the apolipoprotein E system in man Am J Hum Genet 1980 32 339 47 7386461 PMC1686062
  22. [27]Utermann G Steinmetz A Weber W Genetic control of human apolipoprotein E polymorphism: comparison of one- and two-dimensional techniques of isoprotein analysis Hum Genet 1982 60 344 51 7106770
  23. [29]Jain RS Quarfordt SH The carbohydrate content of apolipoprotein E from human very low density lipoproteins Life Sci 1979 25 1315 23 92742
  24. [30]Wernette-Hammond ME Lauer SJ Corsini A Walker D Taylor JM Rall SC Jr Glycosylation of human apolipoprotein E. The carbohydrate attachment site is threonine 194 The Journal of biological chemistry 1989 264 9094 101 2498325
  25. [32]Sivashanmugam A Wang J A unified scheme for initiation and conformational adaptation of human apolipoprotein E N-terminal domain upon lipoprotein binding and for receptor binding activity The Journal of biological chemistry 2009 284 14657 66 19307174 PMC2682913
  26. [33]Forstner M Peters-Libeu C Contreras-Forrest E Newhouse Y Knapp M Rupp B Carboxyl-terminal domain of human apolipoprotein E: expression, purification, and crystallization Protein Expr Purif 1999 17 267 72 10545275
  27. [34]Segrest JP De Loof H Dohlman JG Brouillette CG Anantharamaiah GM Amphipathic helix motif: classes and properties Proteins 1990 8 103 17 2235991
  28. [35]Choy N Raussens V Narayanaswami V Inter-molecular coiled-coil formation in human apolipoprotein E C-terminal domain Journal of molecular biology 2003 334 527 39 14623192
  29. [36]Patel AB Khumsupan P Narayanaswami V Pyrene fluorescence analysis offers new insights into the conformation of the lipoprotein-binding domain of human apolipoprotein E Biochemistry 2010 49 1766 75 20073510
  30. [37]Shore VG Shore B Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components Biochemistry 1973 12 502 7 4345806
  31. [38]Zannis VI Breslow JL Characterization of a unique human apolipoprotein E variant associated with type III hyperlipoproteinemia The Journal of biological chemistry 1980 255 1759 62 7354052
  32. [40]Weisgraber KH Rall SC Jr Mahley RW Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms The Journal of biological chemistry 1981 256 9077 83 7263700
  33. [41]Weisgraber KH Innerarity TL Mahley RW Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site The Journal of biological chemistry 1982 257 2518 21 6277903
  34. [42]Mahley RW Rall SCJ Type III hyperlipoproteinemia (Dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal lipoprotein metabolism Scriver CR Beaudet AL Sly WS Valle D The Metabolic and Molecular Bases of Inherited Disease New York McGraw-Hill Inc 1995 1953 80
  35. [43]Innerarity TL Weisgraber KH Arnold KS Rall SC Jr Mahley RW Normalization of receptor binding of apolipoprotein E2. Evidence for modulation of the binding site conformation The Journal of biological chemistry 1984 259 7261 7 6327714
  36. [44]Dong LM Parkin S Trakhanov SD Rupp B Simmons T Arnold KS Novel mechanism for defective receptor binding of apolipoprotein E2 in type III hyperlipoproteinemia Nature structural biology 1996 3 718 22 8756331
  37. [45]Lalazar A Weisgraber KH Rall SC Jr Giladi H Innerarity TL Levanon AZ Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions The Journal of biological chemistry 1988 263 3542 5 2831187
  38. [47]Wilson PW Relation of high-density lipoprotein subfractions and apolipoprotein E isoforms to coronary disease Clinical chemistry 1995 41 165 9 7813073
  39. [48]Corder EH Saunders AM Strittmatter WJ Schmechel DE Gaskell PC Small GW Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families Science (New York, NY 1993 261 921 3 8346443
  40. [49]Dong LM Weisgraber KH Human apolipoprotein E4 domain interaction. Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins The Journal of biological chemistry 1996 271 19053 7 8702576
  41. [50]Dong LM Wilson C Wardell MR Simmons T Mahley RW Weisgraber KH Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms The Journal of biological chemistry 1994 269 22358 65 8071364
  42. [51]Weers PM Narayanaswami V Choy N Luty R Hicks L Kay CM Lipid binding ability of human apolipoprotein E N-terminal domain isoforms: correlation with protein stability? Biophysical chemistry 2003 100 481 92 12646385
  43. [53]Morrow JA Segall ML Lund-Katz S Phillips MC Knapp M Rupp B Differences in stability among the human apolipoprotein E isoforms determined by the amino-terminal domain Biochemistry 2000 39 11657 66 10995233
  44. [56]Raffai RL Dong LM Farese RV Jr Weisgraber KH Introduction of human apolipoprotein E4 “domain interaction” into mouse apolipoprotein E Proceedings of the National Academy of Sciences of the United States of America 2001 98 11587 91 11553788 PMC58773
  45. [57]Innerarity TL Pitas RE Mahley RW Binding of arginine-rich (E) apoprotein after recombination with phospholipid vesicles to the low density lipoprotein receptors of fibroblasts The Journal of biological chemistry 1979 254 4186 90 220235
  46. [58]Pitas RE Innerarity TL Mahley RW Cell surface receptor binding of phospholipid. protein complexes containing different ratios of receptor-active and -inactive E apoprotein The Journal of biological chemistry 1980 255 5454 60 7372644
  47. [59]Sparrow JT Sparrow DA Culwell AR Gotto AM Jr Apolipoprotein E: phospholipid binding studies with synthetic peptides containing the putative receptor binding region Biochemistry 1985 24 6984 8 3000443
  48. [60]Raussens V Fisher CA Goormaghtigh E Ryan RO Ruysschaert JM The low density lipoprotein receptor active conformation of apolipoprotein E. Helix organization in n-terminal domain-phospholipid disc particles The Journal of biological chemistry 1998 273 25825 30 9748256
  49. [61]Lu B Morrow JA Weisgraber KH Conformational reorganization of the four-helix bundle of human apolipoprotein E in binding to phospholipid The Journal of biological chemistry 2000 275 20775 81 10801877
  50. [62]Narayanaswami V Maiorano JN Dhanasekaran P Ryan RO Phillips MC Lund-Katz S Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles The Journal of biological chemistry 2004 279 14273 9 14739281
  51. [63]Peters-Libeu CA Newhouse Y Hatters DM Weisgraber KH Model of biologically active apolipoprotein E bound to dipalmitoylphosphatidylcholine The Journal of biological chemistry 2006 281 1073 9 16278220
  52. [64]Peters-Libeu CA Newhouse Y Hall SC Witkowska HE Weisgraber KH Apolipoprotein E*dipalmitoylphosphatidylcholine particles are ellipsoidal in solution J Lipid Res 2007 48 1035 44 17308333
  53. [65]Zhang L Song J Newhouse Y Zhang S Weisgraber KH Ren G An optimized negative-staining protocol of electron microscopy for apoE4 POPC lipoprotein J Lipid Res 2010 51 1228 36 19965615 PMC2853450
  54. [67]Fisher CA Narayanaswami V Ryan RO The lipid-associated conformation of the low density lipoprotein receptor binding domain of human apolipoprotein E The Journal of biological chemistry 2000 275 33601 6 10906325
  55. [68]Fisher CA Ryan RO Lipid binding-induced conformational changes in the N-terminal domain of human apolipoprotein E J Lipid Res 1999 40 93 9 9869654
  56. [69]Raussens V Drury J Forte TM Choy N Goormaghtigh E Ruysschaert JM Orientation and mode of lipid-binding interaction of human apolipoprotein E C-terminal domain Biochem J 2005 387 747 54 15588256 PMC1135005
  57. [70]Schneeweis LA Koppaka V Lund-Katz S Phillips MC Axelsen PH Structural analysis of lipoprotein E particles Biochemistry 2005 44 12525 34 16156664
  58. [71]Saito H Dhanasekaran P Nguyen D Holvoet P Lund-Katz S Phillips MC Domain structure and lipid interaction in human apolipoproteins A-I and E, a general model The Journal of biological chemistry 2003 278 23227 32 12709430
  59. [72]Drury J Narayanaswami V Examination of lipid-bound conformation of apolipoprotein E4 by pyrene excimer fluorescence The Journal of biological chemistry 2005 280 14605 10 15708851
  60. [73]Hatters DM Voss JC Budamagunta MS Newhouse YN Weisgraber KH Insight on the molecular envelope of lipid-bound apolipoprotein E from electron paramagnetic resonance spectroscopy Journal of molecular biology 2009 386 261 71 19124026 PMC2665048
  61. [74]Narayanaswami V Ryan RO Molecular basis of exchangeable apolipoprotein function Biochimica et biophysica acta 2000 1483 15 36 10601693
  62. [76]Saito H Dhanasekaran P Baldwin F Weisgraber KH Phillips MC Lund-Katz S Effects of polymorphism on the lipid interaction of human apolipoprotein E The Journal of biological chemistry 2003 278 40723 9 12917433
  63. [77]Davis CG Goldstein JL Sudhof TC Anderson RG Russell DW Brown MS Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region Nature 1987 326 760 5 3494949
  64. [78]Rudenko G Deisenhofer J The low-density lipoprotein receptor: ligands, debates and lore Curr Opin Struct Biol 2003 13 683 9 14675545
  65. [80]Ishibashi S Brown MS Goldstein JL Gerard RD Hammer RE Herz J Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery The Journal of clinical investigation 1993 92 883 93 8349823 PMC294927
  66. [81]Ishibashi S Goldstein JL Brown MS Herz J Burns DK Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice The Journal of clinical investigation 1994 93 1885 93 8182121 PMC294295
  67. [84]Goldstein JL Brown MS The LDL receptor Arteriosclerosis, thrombosis, and vascular biology 2009 29 431 8 PMC2740366 19299327
  68. [85]Mahley RW Weisgraber KH Innerarity T Brewer HB Jr Assmann G Swine lipoproteins and atherosclerosis. Changes in the plasma lipoproteins and apoproteins induced by cholesterol feeding Biochemistry 1975 14 2817 23 167808
  69. [86]Bersot TP Mahley RW Brown MS Goldstein JL Interaction of swine lipoproteins with the low density lipoprotein receptor in human fibroblasts The Journal of biological chemistry 1976 251 2395 8 177413
  70. [87]Mahley RW Innerarity TL Pitas RE Weisgraber KH Brown JH Gross E Inhibition of lipoprotein binding to cell surface receptors of fibroblasts following selective modification of arginyl residues in arginine-rich and B apoproteins The Journal of biological chemistry 1977 252 7279 87 198407
  71. [89]Weisgraber KH Innerarity TL Harder KJ Mahley RW Milne RW Marcel YL The receptor-binding domain of human apolipoprotein E. Monoclonal antibody inhibition of binding The Journal of biological chemistry 1983 258 12348 54 6313653
  72. [90]Lalazar A Mahley RW Human apolipoprotein E. Receptor binding activity of truncated variants with carboxyl-terminal deletions The Journal of biological chemistry 1989 264 8447 50 2542277
  73. [91]Morrow JA Arnold KS Dong J Balestra ME Innerarity TL Weisgraber KH Effect of arginine 172 on the binding of apolipoprotein E to the low density lipoprotein receptor The Journal of biological chemistry 2000 275 2576 80 10644716
  74. [92]Raussens V Slupsky CM Ryan RO Sykes BD NMR structure and dynamics of a receptor-active apolipoprotein E peptide The Journal of biological chemistry 2002 277 29172 80 12036962
  75. [93]Raussens V Slupsky CM Sykes BD Ryan RO Lipid-bound structure of an apolipoprotein E-derived peptide The Journal of biological chemistry 2003 278 25998 6006 12709434
  76. [94]Gupta V Narayanaswami V Budamagunta MS Yamamato T Voss JC Ryan RO Lipid-induced extension of apolipoprotein E helix 4 correlates with low density lipoprotein receptor binding ability The Journal of biological chemistry 2006 281 39294 9 17079229
  77. [95]Funahashi T Yokoyama S Yamamoto A Association of apolipoprotein E with the low density lipoprotein receptor: demonstration of its co-operativity on lipid microemulsion particles J Biochem 1989 105 582 7 2760017
  78. [96]Fisher C Abdul-Aziz D Blacklow SC A two-module region of the low-density lipoprotein receptor sufficient for formation of complexes with apolipoprotein E ligands Biochemistry 2004 43 1037 44 14744149
  79. [97]Rudenko G Henry L Henderson K Ichtchenko K Brown MS Goldstein JL Structure of the LDL receptor extracellular domain at endosomal pH Science (New York, NY 2002 298 2353 8 12459547
  80. [98]Yamamoto T Chen HC Guigard E Kay CM Ryan RO Molecular studies of pH-dependent ligand interactions with the low-density lipoprotein receptor Biochemistry 2008 47 11647 52 18847225 PMC2630525
  81. [99]Beglova N Blacklow SC The LDL receptor: how acid pulls the trigger Trends in biochemical sciences 2005 30 309 17 15950875
  82. [100]Zhao Z Michaely P The epidermal growth factor homology domain of the LDL receptor drives lipoprotein release through an allosteric mechanism involving H190, H562, and H586 The Journal of biological chemistry 2008 283 26528 37 18677035 PMC2546563
  83. [101]Zhao Z Michaely P The role of calcium in lipoprotein release by the low-density lipoprotein receptor Biochemistry 2009 48 7313 24 19583244 PMC2749037
  84. [103]Boyles JK Pitas RE Wilson E Mahley RW Taylor JM Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system The Journal of clinical investigation 1985 76 1501 13 3932467 PMC424114
  85. [105]Xu PT Gilbert JR Qiu HL Ervin J Rothrock-Christian TR Hulette C Specific regional transcription of apolipoprotein E in human brain neurons The American journal of pathology 1999 154 601 11 10027417 PMC1850012
  86. [106]Han SH Einstein G Weisgraber KH Strittmatter WJ Saunders AM Pericak-Vance M Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study Journal of neuropathology and experimental neurology 1994 53 535 44 8083695
  87. [107]Aoki K Uchihara T Sanjo N Nakamura A Ikeda K Tsuchiya K Increased expression of neuronal apolipoprotein E in human brain with cerebral infarction Stroke 2003 34 875 80 12649507
  88. [108]Ladu MJ Reardon C Van Eldik L Fagan AM Bu G Holtzman D Lipoproteins in the central nervous system Annals of the New York Academy of Sciences 2000 903 167 75 10818504
  89. [110]Fagan AM Holtzman DM Astrocyte lipoproteins, effects of apoE on neuronal function, and role of apoE in amyloid-beta deposition in vivo Microsc Res Tech 2000 50 297 304 10936884
  90. [112]Cambon K Davies HA Stewart MG Synaptic loss is accompanied by an increase in synaptic area in the dentate gyrus of aged human apolipoprotein E4 transgenic mice Neuroscience 2000 97 685 92 10842013
  91. [113]Moghadasian MH McManus BM Nguyen LB Shefer S Nadji M Godin DV Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans FASEB J 2001 15 2623 30 11726538
  92. [114]Anderson R Barnes JC Bliss TV Cain DP Cambon K Davies HA Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse Neuroscience 1998 85 93 110 9607706
  93. [115]Anderson R Higgins GA Absence of central cholinergic deficits in ApoE knockout mice Psychopharmacology (Berl) 1997 132 135 44 9266610
  94. [116]Bronfman FC Tesseur I Hofker MH Havekens LM Van Leuven F No evidence for cholinergic problems in apolipoprotein E knockout and apolipoprotein E4 transgenic mice Neuroscience 2000 97 411 8 10828523
  95. [117]Puolivali J Miettinen R Pradier L Riekkinen P Jr Apolipoprotein E-deficient mice are not more susceptible to the biochemical and memory deficits induced by nucleus basalis lesion Neuroscience 2000 96 291 7 10683569
  96. [118]Champagne D Dupuy JB Rochford J Poirier J Apolipoprotein E knockout mice display procedural deficits in the Morris water maze: analysis of learning strategies in three versions of the task Neuroscience 2002 114 641 54 12220566
  97. [119]Oitzl MS Mulder M Lucassen PJ Havekes LM Grootendorst J de Kloet ER Severe learning deficits in apolipoprotein E-knockout mice in a water maze task Brain Res 1997 752 189 96 9106456
  98. [120]Chapman S Sabo T Roses AD Michaelson DM Reversal of presynaptic deficits of apolipoprotein E-deficient mice in human apolipoprotein E transgenic mice Neuroscience 2000 97 419 24 10828524
  99. [121]Gordon I Grauer E Genis I Sehayek E Michaelson DM Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice Neuroscience letters 1995 199 1 4 8584214
  100. [122]Walker LC Parker CA Lipinski WJ Callahan MJ Carroll RT Gandy SE Cerebral lipid deposition in aged apolipoprotein-E-deficient mice The American journal of pathology 1997 151 1371 7 9358763 PMC1858096
  101. [123]Robertson TA Dutton NS Martins RN Roses AD Kakulas BA Papadimitriou JM Age-related congophilic inclusions in the brains of apolipoprotein E-deficient mice Neuroscience 1998 82 171 80 9483513
  102. [124]Mauch DH Nagler K Schumacher S Goritz C Muller EC Otto A CNS synaptogenesis promoted by glia-derived cholesterol Science (New York, NY 2001 294 1354 7 11701931
  103. [125]Goritz C Mauch DH Pfrieger FW Multiple mechanisms mediate cholesterol-induced synaptogenesis in a CNS neuron Mol Cell Neurosci 2005 29 190 201 15911344
  104. [126]Koudinov AR Koudinova NV Cholesterol's role in synapse formation Science (New York, NY 2002 295 2213 11911163
  105. [127]de Chaves EI Rusinol AE Vance DE Campenot RB Vance JE Role of lipoproteins in the delivery of lipids to axons during axonal regeneration The Journal of biological chemistry 1997 272 30766 73 9388216
  106. [128]Posse De Chaves EI Vance DE Campenot RB Kiss RS Vance JE Uptake of lipoproteins for axonal growth of sympathetic neurons The Journal of biological chemistry 2000 275 19883 90 10867025
  107. [129]Ullian EM Christopherson KS Barres BA Role for glia in synaptogenesis Glia 2004 47 209 16 15252809
  108. [130]Thiele C Hannah MJ Fahrenholz F Huttner WB Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles Nat Cell Biol 2000 2 42 9 10620806
  109. [131]Koudinov AR Koudinova NV Essential role for cholesterol in synaptic plasticity and neuronal degeneration FASEB J 2001 15 1858 60 11481254
  110. [132]Rawlins FA Villegas GM Hedley-Whyte ET Uzman BG Fine structural localization of cholesterol-1,2- 3 H in degenerating and regenerating mouse sciatic nerve The Journal of cell biology 1972 52 615 25 5009523 PMC2108665
  111. [133]LeBlanc AC Poduslo JF Regulation of apolipoprotein E gene expression after injury of the rat sciatic nerve J Neurosci Res 1990 25 162 71 2319626
  112. [134]Poirier J Hess M May PC Finch CE Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning Brain Res Mol Brain Res 1991 11 97 106 1661818
  113. [135]Poirier J Baccichet A Dea D Gauthier S Cholesterol synthesis and lipoprotein reuptake during synaptic remodelling in hippocampus in adult rats Neuroscience 1993 55 81 90 8350994
  114. [136]Rawlins FA Hedley-Whyte ET Villegas G Uzman BG Reutilization of cholesterol-1,2-H3 in the regeneration of peripheral nerve. An autoradiographic study Lab Invest 1970 22 237 40 5436517
  115. [137]Boyles JK Notterpek LM Anderson LJ Accumulation of apolipoproteins in the regenerating and remyelinating mammalian peripheral nerve. Identification of apolipoprotein D, apolipoprotein A-IV, apolipoprotein E, and apolipoprotein A-I The Journal of biological chemistry 1990 265 17805 15 2120218
  116. [138]Herz J Apolipoprotein E receptors in the nervous system Curr Opin Lipidol 2009 20 190 6 19433918 PMC2848396
  117. [139]Masliah E Samuel W Veinbergs I Mallory M Mante M Saitoh T Neurodegeneration and cognitive impairment in apoE-deficient mice is ameliorated by infusion of recombinant apoE Brain Res 1997 751 307 14 9099820
  118. [140]Buttini M Orth M Bellosta S Akeefe H Pitas RE Wyss-Coray T Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration J Neurosci 1999 19 4867 80 10366621 PMC6782676
  119. [141]Wang C Wilson WA Moore SD Mace BE Maeda N Schmechel DE Human apoE4-targeted replacement mice display synaptic deficits in the absence of neuropathology Neurobiol Dis 2005 18 390 8 15686968
  120. [142]Ji Y Gong Y Gan W Beach T Holtzman DM Wisniewski T Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer's disease patients Neuroscience 2003 122 305 15 14614898
  121. [143]Jordan BD Genetic influences on outcome following traumatic brain injury Neurochem Res 2007 32 905 15 17342413
  122. [144]Sorbi S Nacmias B Piacentini S Repice A Latorraca S Forleo P ApoE as a prognostic factor for post-traumatic coma Nat Med 1995 1 852 7585199
  123. [145]Teasdale GM Nicoll JA Murray G Fiddes M Association of apolipoprotein E polymorphism with outcome after head injury Lancet 1997 350 1069 71 10213549
  124. [146]Sabo T Lomnitski L Nyska A Beni S Maronpot RR Shohami E Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: the allele E3 is neuroprotective whereas E4 increases fatalities Neuroscience 2000 101 879 84 11113336
  125. [147]Horsburgh K McCulloch J Nilsen M Roses AD Nicoll JA Increased neuronal damage and apoE immunoreactivity in human apolipoprotein E, E4 isoform-specific, transgenic mice after global cerebral ischaemia Eur J Neurosci 2000 12 4309 17 11122341
  126. [148]Boschert U Merlo-Pich E Higgins G Roses AD Catsicas S Apolipoprotein E expression by neurons surviving excitotoxic stress Neurobiol Dis 1999 6 508 14 10600406
  127. [149]Harris FM Tesseur I Brecht WJ Xu Q Mullendorff K Chang S Astroglial regulation of apolipoprotein E expression in neuronal cells. Implications for Alzheimer's disease The Journal of biological chemistry 2004 279 3862 8 14585838
  128. [150]Xu Q Bernardo A Walker D Kanegawa T Mahley RW Huang Y Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus J Neurosci 2006 26 4985 94 16687490 PMC6674234
  129. [151]Huang Y Weisgraber KH Mucke L Mahley RW Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's disease J Mol Neurosci 2004 23 189 204 15181247
  130. [153]Ye S Huang Y Mullendorff K Dong L Giedt G Meng EC Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic target Proceedings of the National Academy of Sciences of the United States of America 2005 102 18700 5 16344478 PMC1311738
  131. [154]Buttini M Masliah E Yu GQ Palop JJ Chang S Bernardo A Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice The American journal of pathology 2010 177 563 9 20595630 PMC2913361
  132. [155]Veinbergs I Mallory M Mante M Rockenstein E Gilbert JR Masliah E Differential neurotrophic effects of apolipoprotein E in aged transgenic mice Neuroscience letters 1999 265 218 22 10327170
  133. [157]Fullerton SM Shirman GA Strittmatter WJ Matthew WD Impairment of the blood-nerve and blood-brain barriers in apolipoprotein e knockout mice Experimental neurology 2001 169 13 22 11312553
  134. [160]Rensink AA de Waal RM Kremer B Verbeek MM Pathogenesis of cerebral amyloid angiopathy Brain Res Brain Res Rev 2003 43 207 23 14572915
  135. [161]Selkoe DJ Alzheimer disease: mechanistic understanding predicts novel therapies Ann Intern Med 2004 140 627 38 15096334
  136. [162]Auld DS Kornecook TJ Bastianetto S Quirion R Alzheimer's disease and the basal forebrain cholinergic system: relations to beta-amyloid peptides, cognition, and treatment strategies Prog Neurobiol 2002 68 209 45 12450488
  137. [163]Strittmatter WJ Weisgraber KH Huang DY Dong LM Salvesen GS Pericak-Vance M Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America 1993 90 8098 102 8367470 PMC47295
  138. [164]Frisoni GB Govoni S Geroldi C Bianchetti A Calabresi L Franceschini G Gene dose of the epsilon 4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzheimer's disease Annals of neurology 1995 37 596 604 7755354
  139. [165]Ishii K Tamaoka A Mizusawa H Shoji S Ohtake T Fraser PE Abeta1-40 but not Abeta1-42 levels in cortex correlate with apolipoprotein E epsilon4 allele dosage in sporadic Alzheimer's disease Brain Res 1997 748 250 2 9067471
  140. [166]Rebeck GW Reiter JS Strickland DK Hyman BT Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions Neuron 1993 11 575 80 8398148
  141. [167]Saunders AM Strittmatter WJ Schmechel D George-Hyslop PH Pericak-Vance MA Joo SH Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease Neurology 1993 43 1467 72 8350998
  142. [170]Fryer JD Demattos RB McCormick LM O'Dell MA Spinner ML Bales KR The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice The Journal of biological chemistry 2005 280 25754 9 15888448
  143. [172]Gong JS Morita SY Kobayashi M Handa T Fujita SC Yanagisawa K Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons Mol Neurodegener 2007 2 9 17504523 PMC1876452
  144. [175]Koldamova R Staufenbiel M Lefterov I Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice The Journal of biological chemistry 2005 280 43224 35 16207713
  145. [176]Wahrle SE Jiang H Parsadanian M Hartman RE Bales KR Paul SM Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease The Journal of biological chemistry 2005 280 43236 42 16207708
  146. [177]Wahrle SE Jiang H Parsadanian M Legleiter J Han X Fryer JD ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE The Journal of biological chemistry 2004 279 40987 93 15269217
  147. [179]Kalaany NY Mangelsdorf DJ LXRS and FXR: the yin and yang of cholesterol and fat metabolism Annu Rev Physiol 2006 68 159 91 16460270
  148. [180]Zelcer N Khanlou N Clare R Jiang Q Reed-Geaghan EG Landreth GE Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors Proceedings of the National Academy of Sciences of the United States of America 2007 104 10601 6 17563384 PMC1890560
  149. [181]Vanmierlo T Rutten K Dederen J Bloks VW van Vark-van der Zee LC Kuipers F Liver X receptor activation restores memory in aged AD mice without reducing amyloid Neurobiol Aging 2009 19674815
  150. [182]Eckert GP Vardanian L Rebeck GW Burns MP Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317 Neuroscience letters 2007 423 47 52 17662526
  151. [183]Riddell DR Zhou H Comery TA Kouranova E Lo CF Warwick HK The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer's disease Mol Cell Neurosci 2007 34 621 8 17336088
  152. [184]Fan J Donkin J Wellington C Greasing the wheels of Abeta clearance in Alzheimer's disease: the role of lipids and apolipoprotein E Biofactors 2009 35 239 48 19472365
  153. [185]Weisgraber KH Mahley RW Human apolipoprotein E: the Alzheimer's disease connection Faseb J 1996 10 1485 94 8940294
  154. [186]Mahley RW Huang Y Apolipoprotein E: from atherosclerosis to Alzheimer's disease and beyond Curr Opin Lipidol 1999 10 207 17 10431657
  155. [187]Xu Q Brecht WJ Weisgraber KH Mahley RW Huang Y Apolipoprotein E4 domain interaction occurs in living neuronal cells as determined by fluorescence resonance energy transfer The Journal of biological chemistry 2004 279 25511 6 15054100
  156. [188]Mahley RW Weisgraber KH Huang Y Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease Proceedings of the National Academy of Sciences of the United States of America 2006 103 5644 51 16567625 PMC1414631
  157. [189]Cho HS Hyman BT Greenberg SM Rebeck GW Quantitation of apoE domains in Alzheimer disease brain suggests a role for apoE in Abeta aggregation Journal of neuropathology and experimental neurology 2001 60 342 9 11305869
  158. [190]Huang Y Liu XQ Wyss-Coray T Brecht WJ Sanan DA Mahley RW Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons Proceedings of the National Academy of Sciences of the United States of America 2001 98 8838 43 11447277 PMC37522
  159. [192]Nakamura T Watanabe A Fujino T Hosono T Michikawa M Apolipoprotein E4 (1-272) fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells Mol Neurodegener 2009 4 35 19695092 PMC2739857
  160. [194]Marques MA Tolar M Harmony JA Crutcher KA A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity Neuroreport 1996 7 2529 32 8981417
  161. [195]Tolar M Marques MA Harmony JA Crutcher KA Neurotoxicity of the 22 kDa thrombin-cleavage fragment of apolipoprotein E and related synthetic peptides is receptor-mediated J Neurosci 1997 17 5678 86 9221767 PMC6573216
  162. [196]Weisgraber KH Roses AD Strittmatter WJ The role of apolipoprotein E in the nervous system Curr Opin Lipidol 1994 5 110 6 8044413
  163. [200]Zhong N Ramaswamy G Weisgraber KH Apolipoprotein E4 domain interaction induces endoplasmic reticulum stress and impairs astrocyte function The Journal of biological chemistry 2009 284 27273 80 19666463 PMC2785655
  164. [201]Zhong N Scearce-Levie K Ramaswamy G Weisgraber KH Apolipoprotein E4 domain interaction: synaptic and cognitive deficits in mice Alzheimers Dement 2008 4 179 92 18631967 PMC2647370
  165. [202]Ramaswamy G Xu Q Huang Y Weisgraber KH Effect of domain interaction on apolipoprotein E levels in mouse brain J Neurosci 2005 25 10658 63 16291938 PMC6725862
  166. [203]Holtzman DM Bales KR Tenkova T Fagan AM Parsadanian M Sartorius LJ Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease Proceedings of the National Academy of Sciences of the United States of America 2000 97 2892 7 10694577 PMC16026
  167. [204]Carter DB Dunn E McKinley DD Stratman NC Boyle TP Kuiper SL Human apolipoprotein E4 accelerates beta-amyloid deposition in APPsw transgenic mouse brain Annals of neurology 2001 50 468 75 11601499
  168. [205]Dodart JC Marr RA Koistinaho M Gregersen BM Malkani S Verma IM Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's-disease Proceedings of the National Academy of Sciences of the United States of America 2005 102 1211 6 15657137 PMC544620
  169. [207]Zhong N Weisgraber KH Understanding the Basis for the Association of Apoe4 with Alzheimer's Disease: Opening the Door for Therapeutic Approaches Curr Alzheimer Res 2009 PMC2810311 19874264
  170. [210]Hardy J Testing times for the “amyloid cascade hypothesis” Neurobiol Aging 2002 23 1073 4 12470803
  171. [211]Golde TE Alzheimer disease therapy: can the amyloid cascade be halted? The Journal of clinical investigation 2003 111 11 8 12511580 PMC151845
  172. [212]Walsh DM Tseng BP Rydel RE Podlisny MB Selkoe DJ The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain Biochemistry 2000 39 10831 9 10978169
  173. [214]Selkoe D Kopan R Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration Annu Rev Neurosci 2003 26 565 97 12730322
  174. [216]Puglielli L Tanzi RE Kovacs DM Alzheimer's disease: the cholesterol connection Nat Neurosci 2003 6 345 51 12658281
  175. [217]Wisniewski T Golabek A Matsubara E Ghiso J Frangione B Apolipoprotein E: binding to soluble Alzheimer's beta-amyloid Biochemical and biophysical research communications 1993 192 359 65 8484748
  176. [218]Wisniewski T Frangione B Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid Neuroscience letters 1992 135 235 8 1625800
  177. [219]Namba Y Tomonaga M Kawasaki H Otomo E Ikeda K Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease Brain Res 1991 541 163 6 2029618
  178. [220]Sanan DA Weisgraber KH Russell SJ Mahley RW Huang D Saunders A Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3 The Journal of clinical investigation 1994 94 860 9 8040342 PMC296168
  179. [221]LaDu MJ Pederson TM Frail DE Reardon CA Getz GS Falduto MT Purification of apolipoprotein E attenuates isoform-specific binding to beta-amyloid The Journal of biological chemistry 1995 270 9039 42 7721816
  180. [223]LaDu MJ Falduto MT Manelli AM Reardon CA Getz GS Frail DE Isoform-specific binding of apolipoprotein E to beta-amyloid The Journal of biological chemistry 1994 269 23403 6 8089103
  181. [224]Nathan BP Bellosta S Sanan DA Weisgraber KH Mahley RW Pitas RE Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro Science (New York, NY 1994 264 850 2 8171342
  182. [225]Tamamizu-Kato S Cohen JK Drake CB Kosaraju MG Drury J Narayanaswami V Interaction with amyloid beta peptide compromises the lipid binding function of apolipoprotein E Biochemistry 2008 47 5225 34 18407659
  183. [226]Shobab LA Hsiung GY Feldman HH Cholesterol in Alzheimer's disease Lancet Neurol 2005 4 841 52 16297842
  184. [227]Poirier J Apolipoprotein E, cholesterol transport and synthesis in sporadic Alzheimer's disease Neurobiol Aging 2005 26 355 61 15639314
  185. [228]Fenili D McLaurin J Cholesterol and apoe: a target for Alzheimer's disease therapeutics Curr Drug Targets CNS Neurol Disord 2005 4 553 67 16266288
  186. [229]Cam JA Bu G Modulation of beta-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family Mol Neurodegener 2006 1 8 16930455 PMC1563464
  187. [230]Bu G Cam J Zerbinatti C LRP in amyloid-beta production and metabolism Annals of the New York Academy of Sciences 2006 1086 35 53 17185504
  188. [231]Wyss-Coray T Loike JD Brionne TC Lu E Anankov R Yan F Adult mouse astrocytes degrade amyloid-beta in vitro and in situ Nat Med 2003 9 453 7 12612547
  189. [233]Cole GM Ard MD Influence of lipoproteins on microglial degradation of Alzheimer's amyloid beta-protein Microsc Res Tech 2000 50 316 24 10936886
  190. [234]Zlokovic BV Clearing amyloid through the blood-brain barrier J Neurochem 2004 89 807 11 15140180
  191. [235]Tanzi RE Moir RD Wagner SL Clearance of Alzheimer's Abeta peptide: the many roads to perdition Neuron 2004 43 605 8 15339642
  192. [236]Deane R Wu Z Sagare A Davis J Du Yan S Hamm K LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms Neuron 2004 43 333 44 15294142
  193. [238]Holtzman DM Bales KR Wu S Bhat P Parsadanian M Fagan AM Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease The Journal of clinical investigation 1999 103 R15 R21 10079115 PMC408154
  194. [239]DeMattos RB Cirrito JR Parsadanian M May PC O'Dell MA Taylor JW ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo Neuron 2004 41 193 202 14741101
  195. [240]Schmechel DE Saunders AM Strittmatter WJ Crain BJ Hulette CM Joo SH Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America 1993 90 9649 53 8415756 PMC47627
  196. [241]Bogdanovic N Corder E Lannfelt L Winblad B APOE polymorphism and clinical duration determine regional neuropathology in Swedish APP(670, 671) mutation carriers: implications for late-onset Alzheimer's disease J Cell Mol Med 2002 6 199 214 12169205 PMC6740279
  197. [242]Bell RD Sagare AP Friedman AE Bedi GS Holtzman DM Deane R Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system J Cereb Blood Flow Metab 2007 27 909 18 17077814 PMC2853021
  198. [243]Roberson ED Scearce-Levie K Palop JJ Yan F Cheng IH Wu T Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model Science (New York, NY 2007 316 750 4 17478722
  199. [244]Tesseur I Van Dorpe J Spittaels K Van den Haute C Moechars D Van Leuven F Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice The American journal of pathology 2000 156 951 64 10702411 PMC1876840
  200. [245]Brecht WJ Harris FM Chang S Tesseur I Yu GQ Xu Q Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice J Neurosci 2004 24 2527 34 15014128 PMC6729489

200 of 202 shown

Authors
Hauser, P. S., Narayanaswami, V., & Ryan, R. O.
Affiliations
  • University of California, Berkeley (US)
  • California State University, Long Beach (US)
Corresponding author
Ryan, Robert O.
ORCID
Venue
Progress in Lipid Research
Publisher
Elsevier BV
Published
2011-01
Volume
50
Issue
1
Pages
62-74
ISSN
0163-7827 (ISSN-L)
DOI
10.1016/j.plipres.2010.09.001
PMC
PMC3022415
OpenAlex
W1973065853
Cited by
320
References
252
Citations by year
2026: 21 · 2025: 20 · 2024: 25 · 2023: 25 · 2022: 25 · 2021: 14 · 2020: 23 · 2019: 17 · 2018: 13 · 2017: 12 · 2016: 13 · 2015: 25 · 2014: 25 · 2013: 30 · 2012: 23
FWCI
1.98
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Progress in Lipid Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • California Tobacco-Related Disease Research Program (16DT-0195, 17RT-0165)
  • National Institutes of Health (HL 64159)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
apolipoprotein E, APOE isoforms, APOE ε4, Alzheimer's disease, cholesterol homeostasis, lipoprotein clearance, low-density lipoprotein receptor family, receptor binding, lipid modification, serum lipoproteins, neurodegenerative diseases, transgenic mouse model
MeSH terms
Alzheimer Disease, Animals, Apolipoproteins E, Biological Transport, Humans, Neurobiology, tau Proteins, Lipid Metabolism

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