Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.
Open accessAbstract
Apolipoprotein E (apoE), a plasma apolipoprotein that plays a central role in lipoprotein metabolism, is localized in the senile plaques, congophilic angiopathy, and neurofibrillary tangles of Alzheimer disease. Late-onset familial and sporadic Alzheimer disease patients have an increased frequency of one of the three common apoE alleles, epsilon 4, suggesting apoE4 is associated with increased susceptibility to disease. To follow up on this suggestion, we compared the binding of synthetic amyloid beta (beta/A4) peptide to purified apoE4 and apoE3, the most common isoform. Both isoforms bound synthetic beta/A4 peptide, the primary constituent of the plaque and angiopathy, forming a complex that resisted dissociation by boiling in SDS. Oxygen-mediated complex formation was implicated because binding was increased in oxygenated buffer, reduced in nitrogen-purged buffer, and prevented by reduction with dithiothreitol or 2-mercaptoethanol. Binding of beta/A4 peptide was saturable at 10(-4) M peptide and required residues 12-28. Examination of apoE fragments revealed that residues 244-272 are critical for complex formation. Both oxidized apoE4 and apoE3 bound beta/A4 peptide; however, binding to apoE4 was observed in minutes, whereas binding to apoE3 required hours. In addition, apoE4 did not bind beta/A4 peptide at pH < 6.6, whereas apoE3 bound beta/A4 peptide from pH 7.6 to 4.6. Together these results indicate differences in the two isoforms in complexing with the beta/A4 peptide. Binding of beta/A4 peptide by oxidized apoE may determine the sequestration or targeting of either apoE or beta/A4 peptide, and isoform-specific differences in apoE binding or oxidation may be involved in the pathogenesis of the intra- and extracellular lesions of Alzheimer disease.
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The literature suggests that there are isoform-dependent differences in ApoE-plaque associations but that several factors, such as ApoE lipidation state, compartment or cell type of origin, and Aβ conformational state, also have important roles in ApoE-Aβ interactions.
“The literature suggests that there are isoform-dependent differences in ApoE–plaque associations but that several factors, such as ApoE lipidation state, compartment or cell type of origin, and Aβ conformational state, also have important roles in ApoE–Aβ interactions52–56.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [52]
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Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Self-citationA Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Self-citationAmyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921 · see citing works
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731 · see citing works
Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E
Wilson, C., Wardell, M. R., Weisgraber, K. H., Mahley, R. W., & Agard, D. A. (1991) · Science · doi:10.1126/science.2063194 · Cited by 678 · see citing works
Self-citationWeisgraber, K. H. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42621-5 · Cited by 304 · see citing works
Self-citationThe receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments.
Innerarity, T. L., Friedlander, E. J., Rall, S. C., Weisgraber, K. H., & Mahley, R. W. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44180-9 · Cited by 276 · see citing works
Self-citationAggerbeck, L. P., Wetterau, J. R., Weisgraber, K. H., Wu, C. S., & Lindgren, F. T. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68779-4 · Cited by 229 · see citing works
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Sorted by citations
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Self-citationAβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938 · see citing works
Oxidative Damage Is the Earliest Event in Alzheimer Disease
Nunomura, A., Perry, G., Aliev, G., Hirai, K., Takeda, A., Balraj, E. K., Jones, P. K., Ghanbari, H., Wataya, T., Shimohama, S., et al. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.8.759 · Cited by 1,885 · see citing works
Apolipoprotein E: Far More Than a Lipid Transport Protein
Mahley, R. W., & Rall, S. C. (2000) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.1.1.507 · Cited by 1,836 · see citing works
Defeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676 · see citing works
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9649 · Cited by 1,525 · see citing works
Self-citationReiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366 · see citing works
Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis
Karch, C. M., & Goate, A. M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.006 · Cited by 1,357 · see citing works
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207 · see citing works
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168 · see citing works
Biomarker Modeling of Alzheimer’s Disease
Jack, C. R., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.12.003 · Cited by 1,002 · see citing works
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943 · see citing works
Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease
Mecocci, P., MacGarvey, U., & Beal, M. F. (1994) · Annals of Neurology · doi:10.1002/ana.410360510 · Cited by 1,037 · see citing works
Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M. E., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12817 · Cited by 1,009 · see citing works
Mahley, R. W., Weisgraber, K. H., & Huang, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600549103 · Cited by 912 · see citing works
Self-citationApolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases
Huang, Y., & Mahley, R. W. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.025 · Cited by 829 · see citing works
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
Holtzman, D. M., Herz, J., & Bu, G. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006312 · Cited by 782 · see citing works
A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Gilman, S., Fox, N. C., Blennow, K., Raskind, M., Sabbagh, M., Honig, L. S., Doody, R., van Dyck, C. H., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67808 · Cited by 753 · see citing works
Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease
Yan, M. H., Wang, X., & Zhu, X. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.014 · Cited by 718 · see citing works
Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk
Efthymiou, A. G., & Goate, A. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0184-x · Cited by 562 · see citing works
ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works
Apolipoprotein E structure: insights into function
Hatters, D. M., Peters-Libeu, C. A., & Weisgraber, K. H. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.06.008 · Cited by 583 · see citing works
Self-citationBlood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease
Erickson, M. A., & Banks, W. A. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.135 · Cited by 572 · see citing works
Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1058 · Cited by 571 · see citing works
Verghese, P. B., Castellano, J. M., Garai, K., Wang, Y., Jiang, H., Shah, A., Bu, G., Frieden, C., & Holtzman, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220484110 · Cited by 556 · see citing works
New insights into the role of TREM2 in Alzheimer’s disease
Gratuze, M., Leyns, C. E. G., & Holtzman, D. M. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0298-9 · Cited by 489 · see citing works
Isoform-specific binding of apolipoprotein E to beta-amyloid.
LaDu, M. J., Falduto, M. T., Manelli, A. M., Reardon, C. A., Getz, G. S., & Frail, D. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31529-6 · Cited by 540 · see citing works
Xu, Q., Bernardo, A., Walker, D., Kanegawa, T., Mahley, R. W., & Huang, Y. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5476-05.2006 · Cited by 524 · see citing works
Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein
Polvikoski, T., Sulkava, R., Haltia, M., Kainulainen, K., Vuorio, A., Verkkoniemi, A., Niinistö, L., Halonen, P., & Kontula, K. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511093331902 · Cited by 493 · see citing works
Bales, K. R., Verina, T., Cummins, D. J., Du, Y., Dodel, R. C., Saura, J., Fishman, C. E., DeLong, C. A., Piccardo, P., Petegnief, V., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15233 · Cited by 486 · see citing works
Apolipoprotein E ε4 allele is associated with deposition of amyloid β-protein following head injury
Nicoll, J. A. R., Roberts, G. W., & Graham, D. I. (1995) · Nature Medicine · doi:10.1038/nm0295-135 · Cited by 486 · see citing works
Strittmatter, W. J., Saunders, A. M., Goedert, M., Weisgraber, K. H., Dong, L. M., Jakes, R., Huang, D. Y., Pericak-Vance, M., Schmechel, D., & Roses, A. D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.11183 · Cited by 474 · see citing works
Self-citationAlzheimer’s Disease Genetics: From the Bench to the Clinic
Karch, C. M., Cruchaga, C., & Goate, A. M. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.041 · Cited by 473 · see citing works
TREM2, microglia, and neurodegenerative diseases
Yeh, F. L., Hansen, D. V., & Sheng, M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.008 · Cited by 440 · see citing works
ApoE and Clusterin Cooperatively Suppress Aβ Levels and Deposition
DeMattos, R. B., Cirrito, J. R., Parsadanian, M., May, P. C., O'Dell, M. A., Taylor, J. W., Harmony, J. A. K., Aronow, B. J., Bales, K. R., Paul, S. M., et al. (2004) · Neuron · doi:10.1016/s0896-6273(03)00850-x · Cited by 459 · see citing works
Perivascular spaces, glymphatic dysfunction, and small vessel disease
Mestre, H., Kostrikov, S., Mehta, R. I., & Nedergaard, M. (2017) · Clinical Science · doi:10.1042/cs20160381 · Cited by 403 · see citing works
Brecht, W. J., Harris, F. M., Chang, S., Tesseur, I., Yu, G.-Q., Xu, Q., Dee Fish, J., Wyss-Coray, T., Buttini, M., Mucke, L., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4315-03.2004 · Cited by 403 · see citing works
Huang, Y., Liu, X. Q., Wyss-Coray, T., Brecht, W. J., Sanan, D. A., & Mahley, R. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151254698 · Cited by 392 · see citing works
Cataldo, A. M., Barnett, J. L., Berman, S. A., Li, J., Quarless, S., Bursztajn, S., Lippa, C., & Nixon, R. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90324-0 · Cited by 379 · see citing works
Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370 · see citing works
Holtzman, D. M., Bales, K. R., Wu, S., Bhat, P., Parsadanian, M., Fagan, A. M., Chang, L. K., Sun, Y., & Paul, S. M. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6179 · Cited by 349 · see citing works
Myers, R. H., Schaefer, E. J., Wilson, P. W. F., D'Agostino, R., Ordovas, J. M., Espino, A., Au, R., White, R. F., Knoefel, J. E., Cobb, J. L., et al. (1996) · Neurology · doi:10.1212/wnl.46.3.673 · Cited by 346 · see citing works
Vascular pathology in the aged human brain
Grinberg, L. T., & Thal, D. R. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0652-7 · Cited by 345 · see citing works
Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases
Vance, J. E. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.010124 · Cited by 342 · see citing works
Harris, F. M., Brecht, W. J., Xu, Q., Tesseur, I., Kekonius, L., Wyss-Coray, T., Fish, J. D., Masliah, E., Hopkins, P. C., Scearce-Levie, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1434398100 · Cited by 342 · see citing works
Self-citationAmyloid β-Peptide Is Transported on Lipoproteins and Albumin in Human Plasma
Biere, A. L., Ostaszewski, B., Stimson, E. R., Hyman, B. T., Maggio, J. E., & Selkoe, D. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32916 · Cited by 331 · see citing works
Dong, L. M., Wilson, C., Wardell, M. R., Simmons, T., Mahley, R. W., Weisgraber, K. H., & Agard, D. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31797-0 · Cited by 320 · see citing works
Self-citationHuman Apolipoprotein E4 Domain Interaction
Dong, L.-M., & Weisgraber, K. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19053 · Cited by 318 · see citing works
Self-citationChang, S., Ma, T. R., Miranda, R. D., Balestra, M. E., Mahley, R. W., & Huang, Y. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508254102 · Cited by 319 · see citing works
Apolipoprotein E, Especially Apolipoprotein E4, Increases the Oligomerization of Amyloid β Peptide
Hashimoto, T., Serrano-Pozo, A., Hori, Y., Adams, K. W., Takeda, S., Banerji, A. O., Mitani, A., Joyner, D., Thyssen, D. H., Bacskai, B. J., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1542-12.2012 · Cited by 294 · see citing works
Aging and Alzheimer's disease: comparison and associations from molecular to system level
Xia, X., Jiang, Q., McDermott, J., & Han, J. J. (2018) · Aging Cell · doi:10.1111/acel.12802 · Cited by 301 · see citing works
Nascent astrocyte particles differ from lipoproteins in CSF
LaDu, M. J., Gilligan, S. M., Lukens, J. R., Cabana, V. G., Reardon, C. A., Van Eldik, L. J., & Holtzman, D. M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052070.x · Cited by 285 · see citing works
Kanekiyo, T., & Bu, G. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00093 · Cited by 281 · see citing works
Ye, S., Huang, Y., Müllendorff, K., Dong, L., Giedt, G., Meng, E. C., Cohen, F. E., Kuntz, I. D., Weisgraber, K. H., & Mahley, R. W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508693102 · Cited by 275 · see citing works
Self-citationAmino- and carboxyl-terminal heterogeneity of β-amyloid peptides deposited in human brain
Saido, T. C., Yamao-Harigaya, W., Iwatsubo, T., & Kawashima, S. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12970-0 · Cited by 270 · see citing works
HDL and cholesterol handling in the brain
Vitali, C., Wellington, C. L., & Calabresi, L. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu148 · Cited by 254 · see citing works
Nagy, Z. S., Esiri, M. M., Jobst, K. A., Johnston, C., Litchfield, S., Sim, E., & Smith, A. D. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00331-c · Cited by 250 · see citing works
Bates, K. A., Verdile, G., Li, Q.-X., Ames, D., Hudson, P., Masters, C. L., & Martins, R. N. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.96 · Cited by 247 · see citing works
Huang, Y., Weisgraber, K. H., Mucke, L., & Mahley, R. W. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:3:189 · Cited by 242 · see citing works
Self-citationThe Development of Amyloid β Protein Deposits in the Aged Brain
Thal, D. R., Capetillo-Zarate, E., Del Tredici, K., & Braak, H. (2006) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2006.6.re1 · Cited by 234 · see citing works
Protection against Alzheimer's disease with apoE ∈2
Talbot, C., Lendon, C., Craddock, N., Shears, S., Morris, J., & Goate, A. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92557-7 · Cited by 225 · see citing works
Genetics of Alzheimer’s disease: where we are, and where we are going
Bellenguez, C., Grenier-Boley, B., & Lambert, J.-C. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.11.024 · Cited by 215 · see citing works
Fagan, A. M., Holtzman, D. M., Munson, G., Mathur, T., Schneider, D., Chang, L. K., Getz, G. S., Reardon, C. A., Lukens, J., Shah, J. A., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30001 · Cited by 222 · see citing works
Gene–environment interactions in Alzheimer disease: the emerging role of epigenetics
Migliore, L., & Coppedè, F. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00714-w · Cited by 217 · see citing works
Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
Cruchaga, C., Kauwe, J. S. K., Nowotny, P., Bales, K., Pickering, E. H., Mayo, K., Bertelsen, S., Hinrichs, A., Fagan, A. M., Holtzman, D. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds296 · Cited by 207 · see citing works
Huynh, T.-P. V., Davis, A. A., Ulrich, J. D., & Holtzman, D. M. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075481 · Cited by 210 · see citing works
Dodart, J.-C., Marr, R. A., Koistinaho, M., Gregersen, B. M., Malkani, S., Verma, I. M., & Paul, S. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409072102 · Cited by 207 · see citing works
Apolipoprotein E and the CNS Response to Injury
Laskowitz, D. T., Horsburgh, K., & Roses, A. D. (1998) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199805000-00001 · Cited by 201 · see citing works
Self-citationStatins for the prevention of dementia
McGuinness, B., Craig, D., Bullock, R., & Passmore, P. (2009) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003160.pub2 · Cited by 193 · see citing works
Basak, J. M., Verghese, P. B., Yoon, H., Kim, J., & Holtzman, D. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.288746 · Cited by 192 · see citing works
Lee, C. Y. D., Tse, W., Smith, J. D., & Landreth, G. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.295451 · Cited by 178 · see citing works
Han, X. (2005) · Current Alzheimer Research · doi:10.2174/1567205052772786 · Cited by 183 · see citing works
Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease.
Gearing, M., Rebeck, G. W., Hyman, B. T., Tigges, J., & Mirra, S. S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.20.9382 · Cited by 179 · see citing works
Ji, Z.-S., Miranda, R. D., Newhouse, Y. M., Weisgraber, K. H., Huang, Y., & Mahley, R. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112109200 · Cited by 177 · see citing works
Self-citationBien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y., & Huang, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0033-12.2012 · Cited by 170 · see citing works
Apolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164 · see citing works
Tai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442103 · Cited by 165 · see citing works
Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade
Honjo, K., Black, S. E., & Verhoeff, N. P. L. G. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100015547 · Cited by 152 · see citing works
Is Alzheimer's disease an apolipoprotein E amyloidosis?
Wisniewski, T., Lalowski, M., Golabek, A., Frangione, B., & Vogel, T. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90701-7 · Cited by 155 · see citing works
Sadowski, M., Pankiewicz, J., Scholtzova, H., Ripellino, J. A., Li, Y., Schmidt, S. D., Mathews, P. M., Fryer, J. D., Holtzman, D. M., Sigurdsson, E. M., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63355-x · Cited by 154 · see citing works
Harris, F. M., Brecht, W. J., Xu, Q., Mahley, R. W., & Huang, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408127200 · Cited by 151 · see citing works
Overlap between neurodegenerative disorders
Armstrong, R. A., Lantos, P. L., & Cairns, N. J. (2005) · Neuropathology · doi:10.1111/j.1440-1789.2005.00605.x · Cited by 146 · see citing works
Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer’s Disease
Cristóvão, J. S., Santos, R., & Gomes, C. M. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/9812178 · Cited by 146 · see citing works
ATP-binding cassette transporter A1: From metabolism to neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.007 · Cited by 144 · see citing works
Roberts, B. R., Lind, M., Wagen, A. Z., Rembach, A., Frugier, T., Li, Q.-X., Ryan, T. M., McLean, C. A., Doecke, J. D., Rowe, C. C., et al. (2017) · Brain · doi:10.1093/brain/awx057 · Cited by 143 · see citing works
Nilsson, L. N. G., Bales, K. R., DiCarlo, G., Gordon, M. N., Morgan, D., Paul, S. M., & Potter, H. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01444.2001 · Cited by 137 · see citing works
ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation
Sen, A., Nelson, T. J., & Alkon, D. L. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.0260-15.2015 · Cited by 133 · see citing works
The Future of Precision Medicine in the Cure of Alzheimer’s Disease
Arafah, A., Khatoon, S., Rasool, I., Khan, A., Rather, M. A., Abujabal, K. A., Faqih, Y. A. H., Rashid, H., Rashid, S. M., Bilal Ahmad, S., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11020335 · Cited by 133 · see citing works
Liao, F., Hori, Y., Hudry, E., Bauer, A. Q., Jiang, H., Mahan, T. E., Lefton, K. B., Zhang, T. J., Dearborn, J. T., Kim, J., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0646-14.2014 · Cited by 128 · see citing works
“The 4 allele of apolipoprotein E (apoE) has been established as the strongest genetic risk factor for late-onset AD (Corder et al., 1993; Strittmatter et al., 1993a; Strittmatter et al., 1993b; Corder et al., 1994; Belinson and Michaelson, 2009).”
BackgroundThe Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease
Kokiko-Cochran, O. N., & Godbout, J. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00672 · Cited by 128 · see citing works
Reactivity of Apolipoprotein E4 and Amyloid β Peptide
Ji, Z.-S., Müllendorff, K., Cheng, I. H., Miranda, R. D., Huang, Y., & Mahley, R. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m506646200 · Cited by 127 · see citing works
Examination of the current top candidate genes for AD in a genome-wide association study
Feulner, T. M., Laws, S. M., Friedrich, P., Wagenpfeil, S., Wurst, S. H. R., Riehle, C., Kuhn, K. A., Krawczak, M., Schreiber, S., Nikolaus, S., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2008.141 · Cited by 128 · see citing works
Tamaki, C., Ohtsuki, S., Iwatsubo, T., Hashimoto, T., Yamada, K., Yabuki, C., & Terasaki, T. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-0208-7 · Cited by 119 · see citing works
Shinohara, M., Fujioka, S., Murray, M. E., Wojtas, A., Baker, M., Rovelet-Lecrux, A., Rademakers, R., Das, P., Parisi, J. E., Graff-Radford, N. R., et al. (2014) · Brain · doi:10.1093/brain/awu046 · Cited by 115 · see citing works
Amino-terminal domain stability mediates apolipoprotein E aggregation into neurotoxic fibrils
Hatters, D. M., Zhong, N., Rutenber, E., & Weisgraber, K. H. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.06.080 · Cited by 105 · see citing works
Self-citationDeeny, S. P., Poeppel, D., Zimmerman, J. B., Roth, S. M., Brandauer, J., Witkowski, S., Hearn, J. W., Ludlow, A. T., Contreras-Vidal, J. L., Brandt, J., et al. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2008.02.007 · Cited by 107 · see citing works
APOE is a major susceptibility gene for Alzheimer’s disease
Roses, A. D., & Saunders, A. M. (1994) · Current Opinion in Biotechnology · doi:10.1016/0958-1669(94)90091-4 · Cited by 108 · see citing works
Self-citation
- Authors
- Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D.
- Affiliations
- Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Durham, NC.
- University of California, San Francisco (US)
- Duke University (US)
- Stony Brook University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1993-09
- Volume
- 90
- Issue
- 17
- Pages
- 8098-8102
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC47295
- OpenAlex
- W2006409771
- Cited by
- 1,363
- References
- 9
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 14 · 2023: 21 · 2022: 38 · 2021: 29 · 2020: 44 · 2019: 32 · 2018: 30 · 2017: 33 · 2016: 34 · 2015: 20 · 2014: 41 · 2013: 31 · 2012: 50
- FWCI
- 53.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- L. K. Whittier Foundation
- National Institutes of Health (5r35ag007922-07)
- National Institute on Aging (5 R35-AG-07922, P50AG005128, 5P50AG05128)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, amyloid-beta, APOE ε4, APOE3, late-onset Alzheimer's disease, protein-protein complex formation, protein oxidation, binding site residues, pH-dependent binding, amyloid plaques
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Electrophoresis, Polyacrylamide Gel, Humans, Peptide Fragments, Protein Binding, Recombinant Proteins, Amyloid beta-Peptides, Apolipoprotein E3, Apolipoprotein E4
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