ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-β1–42
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Amyloid-beta1-42 (Abeta1-42) is crucial to Alzheimer disease (AD) pathogenesis but the conformation of the toxic Abeta species remains uncertain. AD risk is increased by apolipoprotein E4 (apoE4) and decreased by apoE2 compared with the apoE3 isoform, but whether inheritance of apoE4 represents a gain of negative or a loss of protective function is also unresolved. Using hippocampal slices from apoE knockout (apoE-KO) and human apoE2, E3, and E4 targeted replacement (apoE-TR) mice, we found that oligomeric Abeta1-42 inhibited long-term potentiation (LTP) with a hierarchy of susceptibility mirroring clinical AD risk (apoE4-TR > apoE3-TR = apoE-KO > apoE2-TR), and that comparable doses of unaggregated Abeta1-42 did not affect LTP. These data provide a novel link among apoE isoform, Abeta1-42, and a functional cellular model of memory. In this model, apoE4 confers a gain of negative function synergistic with Abeta1-42, apoE2 is protective, and the apoE-Abeta interaction is specific to oligomeric Abeta1-42.
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The APOE2hAβ LTP finding is consistent with observations reported in APOE2-carrying mice but appears paradoxical given APOE2's typical association with neuroprotection in AD.
“This finding is consistent with observations reported in APOE2-carrying mice [82], but appears paradoxical given APOE2’s typical association with neuroprotection in AD [83, 84].”
oAβ-induced deficits in synaptic plasticity are enhanced in the presence of APOE4 compared with APOE2 and APOE3.
“oA-induced deficits in synaptic plasticity (78) and neuronal viability (79) are enhanced in the presence of APOE4 compared with APOE2 and APOE3.”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [78]
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420 · see citing works
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · 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
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
Self-citationProtective 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
Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856 · see citing works
Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201750200 · Cited by 1,452 · see citing works
Self-citationCorrelation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
Näslund, J. (2000) · JAMA · doi:10.1001/jama.283.12.1571 · Cited by 1,268 · see citing works
Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models
Hsia, A. Y., Masliah, E., McConlogue, L., Yu, G.-Q., Tatsuno, G., Hu, K., Kholodenko, D., Malenka, R. C., Nicoll, R. A., & Mucke, L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3228 · Cited by 1,123 · see citing works
Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions
William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T. (1993) · Neuron · doi:10.1016/0896-6273(93)90070-8 · Cited by 1,107 · see citing works
In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis
Stine, W. B., Dahlgren, K. N., Krafft, G. A., & LaDu, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210207200 · Cited by 1,015 · see citing works
Self-citationTargeting small Aβ oligomers: the solution to an Alzheimer's disease conundrum?
Klein, W. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01749-5 · Cited by 989 · see citing works
Increased hippocampal neurogenesis in Alzheimer's disease
Jin, K., Peel, A. L., Mao, X. O., Xie, L., Cottrell, B. A., Henshall, D. C., & Greenberg, D. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2634794100 · Cited by 971 · see citing works
Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
Chapman, P. F., White, G. L., Jones, M. W., Cooper-Blacketer, D., Marshall, V. J., Irizarry, M., Younkin, L., Good, M. A., Bliss, T. V. P., Hyman, B. T., et al. (1999) · Nature Neuroscience · doi:10.1038/6374 · Cited by 946 · see citing works
Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050004797 · Cited by 937 · see citing works
Miyata, M., & Smith, J. D. (1996) · Nature Genetics · doi:10.1038/ng0996-55 · Cited by 889 · see citing works
Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J., et al. (1997) · Nature Genetics · doi:10.1038/ng1197-263 · Cited by 830 · see citing works
β-Amyloid1–42 Binds to α7 Nicotinic Acetylcholine Receptor with High Affinity
Wang, H.-Y., Lee, D. H. S., D’Andrea, M. R., Peterson, P. A., Shank, R. P., & Reitz, A. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5626 · Cited by 818 · see citing works
Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing
Jordan, B. D. (1997) · JAMA · doi:10.1001/jama.278.2.136 · Cited by 659 · see citing works
Poirier, J., Delisle, M.-C., Quirion, R., Aubert, I., Farlow, M. R., Lahiri, D. K., Hui, S. L., Bertrand, P., Nalbantoglu, J. N., & Gilfix, B. M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.26.12260 · Cited by 593 · see citing works
Kirkitadze, M. D., Bitan, G., & Teplow, D. B. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10328 · Cited by 582 · see citing works
Sullivan, P. M., Mezdour, H., Aratani, Y., Knouff, C., Najib, J., Reddick, R. L., Quarfordt, S. H., & Maeda, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17972 · Cited by 575 · see citing works
Self-citationIsoform-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
Self-citationWang, H.-W., Pasternak, J. F., Kuo, H., Ristic, H., Lambert, M. P., Chromy, B., Viola, K. L., Klein, W. L., Stine, W. B., Krafft, G. A., et al. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03058-x · Cited by 527 · see citing works
Self-citationApolipoprotein 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
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
Neuroplasticity Failure in Alzheimer's Disease
Mesulam, M.-M. (1999) · Neuron · doi:10.1016/s0896-6273(00)81109-5 · Cited by 449 · see citing works
Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
(1994) · PubMed Central · Cited by 441 · see citing works
Wang, Q., Walsh, D. M., Rowan, M. J., Selkoe, D. J., & Anwyl, R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1633-03.2004 · Cited by 437 · see citing works
Timing and Location of Nicotinic Activity Enhances or Depresses Hippocampal Synaptic Plasticity
Ji, D., Lape, R., & Dani, J. A. (2001) · Neuron · doi:10.1016/s0896-6273(01)00332-4 · Cited by 419 · see citing works
Palop, J. J., Jones, B., Kekonius, L., Chin, J., Yu, G.-Q., Raber, J., Masliah, E., & Mucke, L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1133381100 · Cited by 402 · see citing works
Lynch, J. R., Tang, W., Wang, H., Vitek, M. P., Bennett, E. R., Sullivan, P. M., Warner, D. S., & Laskowitz, D. T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306923200 · Cited by 394 · see citing works
Self-citationSynaptic pathology in Alzheimer's disease: a review of ultrastructural studies
Scheff, S. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.08.002 · Cited by 391 · see citing works
Progressive age‐related development of Alzheimer‐like pathology in APP/PS1 mice
Trinchese, F., Liu, S., Battaglia, F., Walter, S., Mathews, P. M., & Arancio, O. (2004) · Annals of Neurology · doi:10.1002/ana.20101 · Cited by 369 · see citing works
Buttini, M., Orth, M., Bellosta, S., Akeefe, H., Pitas, R. E., Wyss‐Coray, T., Mucke, L., & Mahley, R. W. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-12-04867.1999 · Cited by 355 · see citing works
Kang, D. E., Pietrzik, C. U., Baum, L., Chevallier, N., Merriam, D. E., Kounnas, M. Z., Wagner, S. L., Troncoso, J. C., Kawas, C. H., Katzman, R., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11013 · Cited by 354 · see citing works
Evans, K. C., Berger, E. P., Cho, C. G., Weisgraber, K. H., & Lansbury, P. T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.3.763 · Cited by 333 · see citing works
Association of apolipoprotein E ϵ2 and vasculopathy in cerebral amyloid angiopathy
Greenberg, S. M., Vonsattel, J.-P. G., Segal, A. Z., Chiu, R. I., Clatworthy, A. E., Liao, A., Hyman, B. T., & Rebeck, G. W. (1998) · Neurology · doi:10.1212/wnl.50.4.961 · Cited by 267 · cited 1× · see citing works
“…well as other clinical disorders that involve amyloid (e.g., cerebral amyloid angiopathy), apoE4 is associated with increased amyloid deposi- tion compared with apoE3 (Deb et al., 2000; Greenberg et al., 1998; Jordan et al., 1997; Nicoll et al., 1995; Polvikoski et al., 1995; Rebeck et al., 1993).”
Tesseur, I. C., Dorpe, J. V., Spittaels, K., den Haute, C. V., Moechars, D., & LEUVEN, F. V. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64963-2 · Cited by 241 · see citing works
Apolipoprotein E and cognitive performance
Raber, J., Wong, D., Yu, G.-Q., Buttini, M., Mahley, R. W., Pitas, R. E., & Mucke, L. (2000) · Nature · doi:10.1038/35006165 · Cited by 237 · see citing works
Block of LTP in rat hippocampus in vivo by β-amyloid precursor protein fragments
Cullen, W. K., Suh, Y., Anwyl, R., & Rowan, M. J. (1997) · Neuroreport · doi:10.1097/00001756-199710200-00006 · Cited by 235 · see citing works
Lanz, T. A., Carter, D. B., & Merchant, K. M. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00079-2 · Cited by 227 · see citing works
Sun, Y., Wu, S., Bu, G., Onifade, M. K., Patel, S. N., LaDu, M. J., Fagan, A. M., & Holtzman, D. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03261.1998 · Cited by 213 · see citing works
Self-citationButtini, M., Yu, G.-Q., Shockley, K., Huang, Y., Jones, B., Masliah, E., Mallory, M., Yeo, T., Longo, F. M., & Mucke, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-24-10539.2002 · Cited by 183 · cited 2× · see citing works
“have also shown that when these mice are crossed with NSE-apoE mice, apoE3 but not apoE4 delays age- and Ah-dependent synaptic and cholinergic deficits and that the mechanism is independent of plaque deposition (Buttini et al., 2002).”
Jordán, J., Galindo, M. F., Miller, R. J., Reardon, C. A., Getz, G. S., & LaDu, M. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-01-00195.1998 · Cited by 178 · see citing works
Self-citationChen, Q.-S., Wei, W., Shimahara, T., & Xie, C.-W. (2002) · Neurobiology of Learning and Memory · doi:10.1006/nlme.2001.4034 · Cited by 176 · see citing works
Ekinci, F. J., Malik, K. U., & Shea, T. B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30322 · Cited by 161 · see citing works
Tolar, M., Keller, J. N., Chan, S., Mattson, M. P., Marques, M. A., & Crutcher, K. A. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-16-07100.1999 · Cited by 148 · see citing works
Apolipoprotein E and Alzheimer Disease: An Update on Genetic and Functional Analyses
Saunders, A. M. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.9.751 · Cited by 148 · see citing works
Grehan, S., Tse, E., & Taylor, J. M. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-03-00812.2001 · Cited by 138 · see citing works
The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease
Tatebayashi, Y., Lee, M. H., Li, L., Iqbal, K., & Grundke, I. (2003) · Acta Neuropathologica · doi:10.1007/s00401-002-0636-3 · Cited by 126 · see citing works
Hartman, R. E., Laurer, H., Longhi, L., Bales, K. R., Paul, S. M., McIntosh, T. K., & Holtzman, D. M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-23-10083.2002 · Cited by 115 · see citing works
ApoE and Aβ1–42 Interactions: Effects of Isoform and Conformation on Structure and Function
Manelli, A. M., Stine, W. B., Van Eldik, L. J., & LaDu, M. J. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:3:235 · Cited by 95 · see citing works
Self-citationNMDA receptor regulation by amyloid-β does not account for its inhibition of LTP in rat hippocampus
Raymond, C. R., Ireland, D. R., & Abraham, W. C. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02269-8 · Cited by 94 · see citing works
Qiu, Z., Crutcher, K., Hyman, B., & Rebeck, G. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.08.017 · Cited by 93 · see citing works
Irizarry, M. C., Cheung, B. S., Rebeck, G. W., Paul, S. M., Bales, K. R., & Hyman, B. T. (2000) · Acta Neuropathologica · doi:10.1007/s004010000263 · Cited by 93 · see citing works
Apolipoprotein E and Alzheimer's disease: the protective effects of ApoE2 and E3
Rebeck, G. W., Kindy, M., & LaDu, M. J. (2002) · Journal of Alzheimer's Disease · doi:10.3233/jad-2002-4304 · Cited by 89 · see citing works
Self-citationInterleukin-1 induces major phenotypic changes in human skin microvascular endothelial cells
Romero, L. I., Zhang, D.-N., Herron, G. S., & Karasek, M. A. (1997) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199710)173:1 · Cited by 88 · see citing works
Zhu, Y., & Hui, D. Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303171200 · Cited by 72 · see citing works
<i>APOE</i> ε4 influences the manifestation of Alzheimer's disease in adults with Down's syndrome
Deb, S., Braganza, J., Norton, N., Williams, H., Kehoe, P. G., Williams, J., & Owen, M. J. (2000) · British Journal of Psychiatry · doi:10.1192/bjp.176.5.468 · Cited by 71 · see citing works
Human apolipoprotein E4 accelerates β‐amyloid deposition in APPsw transgenic mouse brain
Carter, D. B., Dunn, E., McKinley, D. D., Stratman, N. C., Boyle, T. P., Kuiper, S. L., Oostveen, J. A., Weaver, R. J., Boller, J. A., & Gurney, M. E. (2001) · Annals of Neurology · doi:10.1002/ana.1134 · Cited by 67 · see citing works
Modulation of Aβ Deposition in APP Transgenic Mice by an Apolipoprotein E Null Background
IRIZARRY, M. C., REBECK, G. W., CHEUNG, B., BALES, K., PAUL, S. M., HOLZMAN, D., & HYMAN, B. T. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06919.x · Cited by 66 · see citing works
Cambon, K., Davies, H. A., & Stewart, M. G. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00065-8 · Cited by 63 · see citing works
Drouet, B., Fifre, A., Pinçon‐Raymond, M., Vandekerckhove, J. S., Rosseneu, M., Guéant, J., Chambaz, J., & Pillot, T. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00047.x · Cited by 56 · see citing works
Barger, S. W., & Mattson, M. P. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010060.x · Cited by 52 · see citing works
The presence of apoE4, not the absence of apoE3, contributes to AD pathology
Teter, B., Raber, J., Nathan, B., & Crutcher, K. A. (2002) · Journal of Alzheimer's Disease · doi:10.3233/jad-2002-4305 · Cited by 37 · see citing works
Hoffer, M. J. V., Hofker, M. H., van Eck, M. M., Havekes, L. M., & Frants, R. R. (1993) · Genomics · doi:10.1006/geno.1993.1010 · Cited by 26 · see citing works
Impairment of hippocampal long-term potentiation by Alzheimer amyloid ?-peptides
Chen, Q.-S., Kagan, B. L., Hirakura, Y., & Xie, C.-W. (2000) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(20000401)60:1
Flagged first, then by citations
2 of the 72 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Distinct patterns of brain activity in young carriers of the <i>APOE</i> -ε4 allele
Filippini, N., MacIntosh, B. J., Hough, M. G., Goodwin, G. M., Frisoni, G. B., Smith, S. M., Matthews, P. M., Beckmann, C. F., & Mackay, C. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811879106 · Cited by 1,613 · see citing works
Apolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857 · see citing works
Preparing Synthetic Aβ in Different Aggregation States
Stine, W. B., Jungbauer, L., Yu, C., & LaDu, M. J. (2010) · Methods in Molecular Biology · doi:10.1007/978-1-60761-744-0_2 · Cited by 403 · see citing works
Self-citationApolipoprotein E, Receptors, and Modulation of Alzheimer’s Disease
Zhao, N., Liu, C.-C., Qiao, W., & Bu, G. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.03.003 · Cited by 370 · see citing works
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00413-4 · Cited by 306 · see citing works
Huntington's DiseasePreprint
Finkbeiner, S. M. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007476 · Cited by 260 · see citing works
APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease
Youmans, K. L., Tai, L. M., Nwabuisi-Heath, E., Jungbauer, L., Kanekiyo, T., Gan, M., Kim, J., Eimer, W. A., Estus, S., Rebeck, G. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407957 · Cited by 259 · see citing works
“Prior work from our laboratory demonstrates that oA -induced deficits in synaptic plasticity (78) and neuronal viability (79) are enhanced in the presence ofAPOE4 comparedwithAPOE2 and APOE3.”
BackgroundSelf-citationRiddell, D. R., Zhou, H., Comery, T. A., Kouranova, E., Lo, C. F., Warwick, H. K., Ring, R. H., Kirksey, Y., Aschmies, S., Xu, J., et al. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.01.011 · Cited by 244 · see citing works
Mirochnic, S., Wolf, S. A., Staufenbiel, M., & Kempermann, G. (2009) · Hippocampus · doi:10.1002/hipo.20560 · Cited by 208 · see citing works
Kumar, A. (2011) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2011.00007 · Cited by 169 · see citing works
Reelin signaling antagonizes β-amyloid at the synapse
Durakoglugil, M. S., Chen, Y., White, C. L., Kavalali, E. T., & Herz, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908176106 · Cited by 153 · see citing works
Kim, J., Yoon, H., Basak, J., & Kim, J. (2014) · Molecules and Cells · doi:10.14348/molcells.2014.0248 · Cited by 141 · see citing works
“…LTP was inhibited by oligomeric a 1-42 with susceptibility of; apoE4 > apoE3 = apoE KO > apoE2 2-4 apoE4: gain of negative function apoE2: loss of protective function (Trommer et al., 2005) Human apoE3,E4 KI endogenous ApoE4 KI exhibited deficits in RAM, which was improved after exercise.”
BackgroundRETRACTED: Cognitive effects of cell-derived and synthetically derived Aβ oligomers
Reed, M. N., Hofmeister, J. J., Jungbauer, L. M., Welzel, A. T., Yu, C., Sherman, M. A., Lesné, S., LaDu, M. J., Walsh, D. M., Ashe, K. H., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.11.007 · Cited by 132 · see citing works
Self-citationRetractedBour, A., Grootendorst, J., Vogel, E., Kelche, C., Dodart, J.-C., Bales, K., Moreau, P.-H., Sullivan, P. M., & Mathis, C. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.05.008 · Cited by 141 · see citing works
Self-citationSynaptic tau: A pathological or physiological phenomenon?
Robbins, M., Clayton, E. L., & Schierle, G. S. K. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01246-y · Cited by 117 · see citing works
Reduced levels of human apoE4 protein in an animal model of cognitive impairment
Sullivan, P. M., Han, B., Liu, F., Mace, B. E., Ervin, J. F., Wu, S., Koger, D., Paul, S., & Bales, K. R. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.05.011 · Cited by 113 · see citing works
Self-citationSynaptic targeting by Aβ oligomers (ADDLS) as a basis for memory loss in early Alzheimer's disease
Klein, W. L. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2005.11.003 · Cited by 107 · see citing works
Delineating the Mechanism of Alzheimer’s Disease Aβ Peptide Neurotoxicity
Cappai, R., & Barnham, K. J. (2008) · Neurochemical Research · doi:10.1007/s11064-007-9469-8 · Cited by 108 · see citing works
Johnson, L. A., Olsen, R. H. J., Merkens, L. S., DeBarber, A. E., Steiner, R. D., Sullivan, P. M., Maeda, N., & Raber, J. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.12.016 · Cited by 105 · see citing works
Self-citationThe Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease
Nowak, A., Kojder, K., Zielonka-Brzezicka, J., Wróbel, J., Bosiacki, M., Fabiańska, M., Wróbel, M., Sołek-Pastuszka, J., & Klimowicz, A. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.775034 · Cited by 105 · see citing works
Liu, D.-S., Pan, X.-D., Zhang, J., Shen, H., Collins, N. C., Cole, A. M., Koster, K. P., Ben Aissa, M., Dai, X.-M., Zhou, M., et al. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0002-2 · Cited by 99 · see citing works
Self-citationEFAD transgenic mice as a human APOE relevant preclinical model of Alzheimerʼns disease
Tai, L. M., Balu, D., Avila-Munoz, E., Abdullah, L., Thomas, R., Collins, N., Valencia-Olvera, A. C., & LaDu, M. J. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r076315 · Cited by 93 · see citing works
Self-citationApoE isoform-dependent changes in hippocampal synaptic function
Korwek, K. M., Trotter, J. H., LaDu, M. J., Sullivan, P. M., & Weeber, E. J. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-21 · Cited by 89 · see citing works
Self-citationModes of Aβ toxicity in Alzheimer’s disease
Götz, J., Eckert, A., Matamales, M., Ittner, L. M., & Liu, X. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0750-2 · Cited by 84 · see citing works
Zhao, J., Fu, Y., Liu, C., Shinohara, M., Nielsen, H. M., Dong, Q., Kanekiyo, T., & Bu, G. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.526095 · Cited by 70 · see citing works
Jungbauer, L. M., Yu, C., Laxton, K., & LaDu, M. J. (2009) · Journal of Molecular Recognition · doi:10.1002/jmr.948 · Cited by 73 · see citing works
Self-citationAβ42 neurotoxicity in primary co-cultures: effect of apoE isoform and Aβ conformation
Manelli, A. M., Bulfinch, L. C., Sullivan, P. M., & LaDu, M. J. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.024 · Cited by 72 · see citing works
Self-citationChan, A., & Shea, T. B. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04589.x · Cited by 71 · see citing works
The generation and function of soluble apoE receptors in the CNS
Rebeck, G. W., LaDu, M. J., Estus, S., Bu, G., & Weeber, E. J. (2006) · Molecular Neurodegeneration · doi:10.1186/1750-1326-1-15 · Cited by 66 · see citing works
Self-citationKlein, R. C., Mace, B. E., Moore, S. D., & Sullivan, P. M. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.10.027 · Cited by 67 · see citing works
Self-citationIntracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer’s Disease
Perdigão, C., Barata, M. A., Araújo, M. N., Mirfakhar, F., Castanheira, J., & Almeida, C. G. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00072 · Cited by 56 · see citing works
The functional neurophysiology of the amyloid precursor protein (APP) processing pathway
Randall, A. D., Witton, J., Booth, C., Hynes-Allen, A. M., & Brown, J. T. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.02.011 · Cited by 64 · see citing works
Zheng, Z.-Q., Sabirzhanov, B., & Keifer, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.150821 · Cited by 61 · see citing works
Chernick, D., Ortiz-Valle, S., Jeong, A., Qu, W., & Li, L. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134306 · Cited by 54 · see citing works
Endocytic pathways mediating oligomeric Aβ42 neurotoxicity
Yu, C., Nwabuisi‐Heath, E., Laxton, K., & LaDu, M. J. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-19 · Cited by 61 · see citing works
Self-citation<scp>APOE</scp> genotype affects the pre‐synaptic compartment of glutamatergic nerve terminals
Dumanis, S. B., DiBattista, A. M., Miessau, M., Moussa, C. E. H., & Rebeck, G. W. (2013) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07908.x · Cited by 55 · see citing works
Amyloid-beta1–42 reduces neuronal excitability in mouse dentate gyrus
Yun, S. H., Gamkrelidze, G. N., Stine, W. B., Sullivan, P. M., Pasternak, J. F., LaDu, M. J., & Trommer, B. L. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.04.065 · Cited by 57 · see citing works
Self-citationDong, W., Vuletic, S., & Albers, J. J. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m900236-jlr200 · Cited by 56 · see citing works
Plasma Signaling Proteins in Persons at Genetic Risk for Alzheimer Disease
Ringman, J. M., Elashoff, D. A., Geschwind, D. H., Welsh, B. T., Gylys, K. H., Lee, C., Cummings, J. L., & Cole, G. M. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.277 · Cited by 55 · see citing works
Reelin and apoE actions on signal transduction, synaptic function and memory formation
Rogers, J. T., & Weeber, E. J. (2008) · Neuron Glia Biology · doi:10.1017/s1740925x09990184 · Cited by 49 · see citing works
Understanding heterogeneity in the effects of birth weight on adult cognition and wages
Cook, C. J., & Fletcher, J. M. (2015) · Journal of Health Economics · doi:10.1016/j.jhealeco.2015.01.005 · Cited by 47 · see citing works
Emergence of a seizure phenotype in aged apolipoprotein epsilon 4 targeted replacement mice
Hunter, J. M., Cirrito, J. R., Restivo, J. L., Kinley, R. D., Sullivan, P. M., Holtzman, D. M., Koger, D., Delong, C., Lin, S., Zhao, L., et al. (2012) · Brain Research · doi:10.1016/j.brainres.2012.05.048 · Cited by 45 · see citing works
Self-citationMaioli, S., Puerta, E., Merino‐Serrais, P., Fusari, L., Gil-Bea, F. J., Rimondini, R., & Cedazo-Mı́nguez, Á. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120697 · Cited by 44 · see citing works
Nenov, M. N., Tempia, F., Denner, L. A., Dineley, K. T., & Laezza, F. (2014) · Journal of Neurophysiology · doi:10.1152/jn.00419.2014 · Cited by 42 · see citing works
Raman, S., Brookhouser, N., & Brafman, D. A. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104788 · Cited by 40 · see citing works
A β‐amyloid oligomer directly modulates P/Q‐type calcium currents inXenopusoocytes
Mezler, M., Barghorn, S., Schoemaker, H., Gross, G., & Nimmrich, V. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01646.x · Cited by 40 · see citing works
An update on the toxicity of Aβ in Alzheimer’s disease
Götz, J. (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s3016 · Cited by 39 · see citing works
APOE genotype determines cell-type-specific pathological landscape of Alzheimer’s disease
Li, Z., Martens, Y. A., Ren, Y., Jin, Y., Sekiya, H., Doss, S. V., Kouri, N., Castanedes-Casey, M., Christensen, T. A., Miller Nevalainen, L. B., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.02.017 · Cited by 39 · see citing works
Cerebral Arachidonate Cascade in Dementia: Alzheimers Disease and Vascular Dementia
Yagami, T. (2005) · Current Neuropharmacology · doi:10.2174/157015906775203011 · Cited by 38 · see citing works
Granic, I., Nyakas, C. J., Luiten, P. G. M., Eisel, U. L. M., Halmy, L. G., Groß, G., Schoemaker, H., Möller, A., & Nimmrich, V. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.07.013 · Cited by 36 · see citing works
Estradiol enhances long term potentiation in hippocampal slices from aged apoE4‐TR mice
Yun, S. H., Park, K. A., Kwon, S. E., Woolley, C. S., Sullivan, P. M., Pasternak, J. F., & Trommer, B. L. (2007) · Hippocampus · doi:10.1002/hipo.20357 · Cited by 34 · see citing works
Self-citationDecisive role of Reelin signaling during early stages of Alzheimer’s disease
Krstic, D., Pfister, S., Notter, T., & Knuesel, I. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.042 · Cited by 33 · see citing works
Dietary Supplementation with Apple Juice Decreases Endogenous Amyloid-β Levels in Murine Brain
Chan, A., & Shea, T. B. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0959 · Cited by 29 · see citing works
Endomorphin‐2, an endogenous tetrapeptide, protects against Aβ1‐42 in vitro and in vivo
Szegedi, V., Juhász, G., Rozsa, É., Juhász-Vedres, G., Datki, Z., Fülöp, L., Bozsó, Z., Lakatos, A., Laczkó, I., Farkas, T., et al. (2006) · The FASEB Journal · doi:10.1096/fj.05-4891fje · Cited by 28 · see citing works
APOE ε4 is associated with higher levels of CSF SNAP-25 in prodromal Alzheimer’s disease
Wang, S., Zhang, J., & Pan, T. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.08.029 · Cited by 27 · see citing works
Smith, J. P., Lal, V., Bowser, D. N., Cappai, R., Masters, C. L., & Ciccotosto, G. D. (2009) · Brain Research · doi:10.1016/j.brainres.2009.03.007 · Cited by 27 · see citing works
Yun, S. H., Park, K. A., Sullivan, P. M., Pasternak, J. F., LaDu, M. J., & Trommer, B. L. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20684 · Cited by 27 · see citing works
Self-citationMhatre‐Winters, I., Eid, A., Han, Y., Tieu, K., & Richardson, J. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179829 · Cited by 26 · see citing works
High-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22 · see citing works
Klein, W. L., Lacor, P. N., Felice, F. G. D., & Ferreira, S. T. (2007) · Research and perspectives in neurosciences · doi:10.1007/978-3-540-45702-2_11 · Cited by 23 · see citing works
Apolipoprotein E in Alzheimer’s Disease: Focus on Synaptic Function and Therapeutic Strategy
Qu, L., Xu, S., Lan, Z., Fang, S., Xu, Y., & Zhu, X. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04449-1 · Cited by 22 · see citing works
Valencia‐Olvera, A. C., Balu, D., Faulk, N., Amiridis, A., Wang, Y., Pham, C., Avila-Munoz, E., York, J. M., Thatcher, G. R. J., & LaDu, M. J. (2023) · Neurotherapeutics · doi:10.1007/s13311-023-01375-3 · Cited by 22 · see citing works
Self-citationPedrini, S., Doecke, J. D., Hone, E., Wang, P., Thota, R. N., Bush, A. I., Rowe, C. C., Doré, V., Villemagne, V. L., Ames, D. J., et al. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15681 · Cited by 19 · see citing works
Belinson, H., & Michaelson, D. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1065 · Cited by 14 · see citing works
Klonarakis, M., Vos, M. D., Woo, E. K., Ralph, L. T., Thacker, J. S., & Gil‐Mohapel, J. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104541 · Cited by 13 · see citing works
Greco, G. A., Rock, M. B., Amontree, M., Lanfranco, M. F., Korthas, H. T., Hong, S. H., Turner, R. S., Rebeck, G. W., & Conant, K. E. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106057 · Cited by 11 · see citing works
Yesiltepe, M., Yin, T., Tambini, M., Bao, H., Pan, M., d’Abramo, C., Giliberto, L., Han, X., & D’Adamio, L. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01832-2 · Cited by 10 · see citing works
“This finding is consistent with observations reported in APOE2-carrying mice [82], but appears paradoxical given APOE2’s typical association with neuroprotection in AD [83, 84].”
ResultMolecular Determinants of Alzheimer’s Disease Aβ Peptide Neurotoxicity
Cappai, R., & Barnham, K. J. (2007) · Future Neurology · doi:10.2217/14796708.2.4.397 · Cited by 9 · see citing works
Wu, M., He, Y., Zhang, J., Yang, J., & Qi, J. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.03.043 · Cited by 6 · see citing works
Apolipoprotein E3 as a Risk Factor for Alzheimer's Disease Under Conditions of Nutritional Imbalance
Chan, A., & Shea, T. B. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100060 · Cited by 4 · see citing works
Molecular Aspects of Memory Dysfunction in Alzheimer’s Disease
Chin, J., Roberson, E. D., & Mucke, L. (2008) · Elsevier eBooks · doi:10.1016/b978-012370509-9.00015-2 · Cited by 4 · see citing works
Higher Neuronal Facilitation and Potentiation with APOE4 Suppressed by Angiotensin II
Scheinman, S. B., Tseng, K. Y., Alford, S. T., & Tai, L. M. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03556-9 · Cited by 3 · see citing works
Neuron-specific susceptibility to apolipoprotein E4
Belinson, H., Dolev, I., & Michaelson, D. M. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.06.027 · Cited by 2 · see citing works
APOE-Based Models of “Pre-Dementia”
Sullivan, P. M. (2010) · Neuromethods · doi:10.1007/978-1-60761-898-0_22 · Cited by 1 · see citing works
Self-citationStephens, G. S., You, J. C., Fu, C.-H., & Chin, J. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.21126-7 · Cited by 1 · see citing works
Koutseff, A. (2011) · OpenGrey (Institut de l'Information Scientifique et Technique)
Synaptic Pathology in Dementia
Scheff, S. W. (2006) · Springer eBooks · doi:10.1007/978-0-387-32562-0_30
ERP-based Detection of Brain Pathology in Rat Models for Preclinical Alzheimer's Disease
Nouriziabari, S. B. (2016) · TSpace (University of Toronto)
Microscopical, phytochemical, and LC/MS analysis of Ginkgo biloba leaves
Eldalawy, R., Nasser, N. M., & Hussein, A. M. (2024) · Plant Science Today · doi:10.14719/pst.3097
Additional file 1 of Synaptic tau: A pathological or physiological phenomenon?
Robbins, M., Clayton, E. L., & Schierle, G. S. K. (2021) · Figshare · doi:10.6084/m9.figshare.16599510
- Authors
- Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Blaine Stine, W., Manelli, A., Sullivan, P., Pasternak, J. F., & LaDu, M. J.
- Affiliations
- Northwestern University (US)
- Duke University (US)
- Corresponding author
- Trommer, Barbara L.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 18
- Issue
- 1
- Pages
- 75-82
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2055766521
- Cited by
- 82
- References
- 72
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 5
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (AG18121)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- apolipoprotein E isoforms, amyloid-beta 42, amyloid-beta oligomers, long-term potentiation, Alzheimer's disease, APOE ε4, APOE2, APOE3, hippocampus, memory
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Cell Survival, Hippocampus, Male, Mice, Transgenic, Molecular Weight, Organ Culture Techniques, Peptide Fragments, Protein Conformation, Amyloid beta-Peptides, Long-Term Potentiation, Mice, Knockout, Neuroprotective Agents, Protein Isoforms, Mice, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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