Human APOE genotype affects intraneuronal A 1-42 accumulation in a lentiviral gene transfer model

Zhao, W.; Dumanis, S. B.; Tamboli, I. Y.; Rodriguez, G. A.; Jo LaDu, M.; Moussa, C. E. H.; William Rebeck, G.

doi:10.1093/hmg/ddt525

Cited by 32Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Human APOE genotype affects intraneuronal A 1-42 accumulation in a lentiviral gene transfer model

Open access

Zhao, W., Dumanis, S. B., Tamboli, I. Y., Rodriguez, G. A., Jo LaDu, M., Moussa, C. E. H., William Rebeck, G.·2014·Human Molecular Genetics

DOI 10.1093/hmg/ddt525PMC PMC3919009

Open this paper in CoChat — free account

Abstract

Intraneuronal accumulation of β-amyloid (Aβ)42 is one of the earliest pathological events in humans and in animal models of Alzheimer's disease (AD). Apolipoprotein E 4 (APOE4) is the major identified genetic risk factor for late-onset AD, with Aβ deposition beginning earlier in apoE4-positive subjects. To directly determine the effects of APOE genotype on intraneuronal accumulation of Aβ1-42 at the onset of AD pathogenesis, we introduced lentiviral Aβ1-42 into the cortex of APOE targeted replacement (TR) mice at the age of 8-9 months. We demonstrated a significant isoform-dependent effect of human APOE, with dramatically enhanced intracellular Aβ1-42 deposits in the cerebral cortex of APOE4-TR mice 2 weeks after injection. Double-immunofluorescent staining showed that intracellular accumulation of lentiviral Aβ1-42 was mainly present in neurons, localized to late endosomes/lysosomes. This intraneuronal accumulation of Aβ1-42 correlated with increased tau phosphorylation and cell death in the ipsilateral cortex around the injection site. Aβ1-42 was also observed in microglia, but not in astrocytes. Quantitative analysis revealed more neurons with Aβ1-42 while less microglia with Aβ1-42 nearest to the injection site of Aβ1-42 lentivirus in APOE4-TR mice. Finally, apoE was present in neurons of the ipsilateral cortex of APOE-TR mice at 2 weeks after lentivirus injection, in addition to astrocytes and microglia in both the ipsilateral and contralateral cerebral cortex. Taken together, these results demonstrate that apoE4 tips the balance of the glial and neuronal Aβ toward the intraneuronal accumulation of Aβ.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1093/hmg/ddt525

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Lentiviral expression of human APOE4 in AD mouse brain increases ISF-oAβ levels and aggravates plaque deposition, while APOE2 reduces Aβ accumulation.
“Lentiviral expression of human APOE4 in AD mouse brain also increased ISF -oAβ levels and aggravated plaque deposition, while APOE2 was observed to reduce Aβ accumulation [457, 458].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [457]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · see citing works
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
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
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490 · see citing works
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459 · see citing works
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078 · see citing works
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942 · 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
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
Alzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424 · see citing works
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,227 · 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
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
Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease
Jack, C. R., Lowe, V. J., Weigand, S. D., Wiste, H. J., Senjem, M. L., Knopman, D. S., Shiung, M. M., Gunter, J. L., Boeve, B. F., Kemp, B. J., et al. (2009) · Brain · doi:10.1093/brain/awp062 · Cited by 1,099 · see citing works
Intraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991 · see citing works
ApoE Promotes the Proteolytic Degradation of Aβ
Jiang, Q., Lee, C. Y. D., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T. M., Collins, J. L., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.010 · Cited by 876 · see citing works
Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease
Reiman, E. M., Chen, K., Liu, X., Bandy, D., Yu, M., Lee, W., Ayutyanont, N., Keppler, J., Reeder, S. A., Langbaum, J. B. S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900345106 · Cited by 785 · 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
Lysosomes in cell death
Guicciardi, M. E., Leist, M., & Gores, G. J. (2004) · Oncogene · doi:10.1038/sj.onc.1207512 · Cited by 716 · see citing works
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · see citing works
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · cited 1× · see citing works
“Ab42 represents 10% of synthesized Ab, but is the earliest and predominant Ab species deposited in plaques in AD (8).”
Background
Microglial Cells Internalize Aggregates of the Alzheimer's Disease Amyloid β-Protein Via a Scavenger Receptor
Paresce, D. M., Ghosh, R. N., & Maxfield, F. R. (1996) · Neuron · doi:10.1016/s0896-6273(00)80187-7 · Cited by 663 · see citing works
Targeted Replacement of the Mouse Apolipoprotein E Gene with the Common Human APOE3 Allele Enhances Diet-induced Hypercholesterolemia and Atherosclerosis
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
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
Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice
McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.030 · Cited by 565 · see citing works
Clearing the brain's amyloid cobwebs
Selkoe, D. J. (2001) · Neuron · doi:10.1016/s0896-6273(01)00475-5 · Cited by 541 · 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
Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus
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
Identification of two lysosomal membrane glycoproteins.
Chen, J. W., Murphy, T. L., Willingham, M. C., Pastan, I. H., & August, J. T. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.101.1.85 · Cited by 485 · see citing works
Microglial Phagocytosis of Fibrillar β-Amyloid through a β1Integrin-Dependent Mechanism
Koenigsknecht-Talboo, J., & Landreth, G. E. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2557-04.2004 · Cited by 444 · see citing works
Microglia Mediate the Clearance of Soluble Aβ through Fluid Phase Macropinocytosis
Mandrekar, S., Jiang, Q., Lee, C. Y. D., Koenigsknecht-Talboo, J., Holtzman, D. M., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5572-08.2009 · Cited by 415 · see citing works
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372 · see citing works
The Dynamics of Autophagy Visualised in Live Cells: from Autophagosome Formation to Fusion with Endo/lysosomes
Bampton, E. T. W., Goemans, C. G., Niranjan, D., Mizushima, N., & Tolkovsky, A. M. (2005) · Autophagy · doi:10.4161/auto.1.1.1495 · Cited by 369 · see citing works
Apo E structure determines VLDL clearance and atherosclerosis risk in mice
Knouff, C., Hinsdale, M. E., Mezdour, H., Altenburg, M. K., Watanabe, M., Quarfordt, S. H., Sullivan, P. M., & Maeda, N. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6172 · Cited by 324 · see citing works
Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance
Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274 · see citing works
Human<i>APOE</i>Isoform-Dependent Effects on Brain β-Amyloid Levels in PDAPP Transgenic Mice
Bales, K. R., Liu, F., Wu, S., Lin, S., Koger, D., DeLong, C., Hansen, J. C., Sullivan, P. M., & Paul, S. M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0887-09.2009 · Cited by 274 · see citing works
Intracellular accumulation of amyloid-beta – a predictor for synaptic dysfunction and neuron loss in Alzheimer’s disease
Bayer (2010) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2010.00008 · Cited by 252 · see citing works
Inflammation in the early stages of neurodegenerative pathology
Khandelwal, P. J., Herman, A. M., & Moussa, C. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.07.002 · Cited by 211 · see citing works
Self-citation
Lysosomal Membrane Damage in Soluble Aβ-Mediated Cell Death in Alzheimer's Disease
Ditaranto, K., Tekirian, T. L., & Yang, A. J. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0364 · Cited by 192 · see citing works
Specific Regional Transcription of Apolipoprotein E in Human Brain Neurons
Xu, P., Gilbert, J. R., Qiu, H.-L., Ervin, J. F., Rothrock‐Christian, T., Hulette, C., & Schmechel, D. E. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65305-9 · Cited by 177 · see citing works
Apolipoprotein E4 Potentiates Amyloid β Peptide-induced Lysosomal Leakage and Apoptosis in Neuronal Cells
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
Differential Regulation of Amyloid-β Endocytic Trafficking and Lysosomal Degradation by Apolipoprotein E Isoforms
Li, J., Kanekiyo, T., Shinohara, M., Zhang, Y., LaDu, M. J., Xu, H., & Bu, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.420224 · Cited by 175 · see citing works
Intraneuronal Aβ detection in 5xFAD mice by a new Aβ-specific antibody
Youmans, K. L., Tai, L. M., Kanekiyo, T., Stine Jr, W. B., Michon, S.-C., Nwabuisi-Heath, E., Manelli, A. M., Fu, Y., Riordan, S., Eimer, W. A., et al. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-8 · Cited by 164 · see citing works
Parkin Ubiquitinates Tar-DNA Binding Protein-43 (TDP-43) and Promotes Its Cytosolic Accumulation via Interaction with Histone Deacetylase 6 (HDAC6)
Hebron, M. L., Lonskaya, I., Sharpe, K., Weerasinghe, P. P. K., Algarzae, N. K., Shekoyan, A. R., & Moussa, C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.419945 · Cited by 138 · see citing works
Self-citation
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
The Pro-Neurotrophin Receptor Sortilin Is a Major Neuronal Apolipoprotein E Receptor for Catabolism of Amyloid-β Peptide in the Brain
Carlo, A.-S., Gustafsen, C., Mastrobuoni, G., Nielsen, M. S., Burgert, T., Hartl, D., Rohe, M., Nykjær, A., Herz, J., Heeren, J., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2425-12.2013 · Cited by 109 · see citing works
Apolipoprotein E promotes the binding and uptake of β-amyloid into Chinese hamster ovary cells in an isoform-specific manner
Yang, D.-S., Small, D. H., Seydel, U., Smith, J. D., Hallmayer, J. F., Gandy, S., & Martins, R. N. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00561-2 · Cited by 108 · see citing works
Activation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits
Belinson, H., Lev, D., Masliah, E., & Michaelson, D. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5633-07.2008 · Cited by 101 · cited 2× · see citing works
“Inhibition of Ab-degrading enzyme neprilysin in APOE3 and APOE4 mice led to an apoE4 isoform-specific accumulation of intraneuronal Ab, accompanied by intracellular apoE and lysosomal activation (47).”
Background
Parkin promotes intracellular A 1-42 clearance
Burns, M. P., Zhang, L., Rebeck, G. W., Querfurth, H. W., & Moussa, C. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp258 · Cited by 98 · see citing works
Self-citation
Aβ Internalization by Neurons and Glia
Mohamed, A., & Chaves, E. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/127984 · Cited by 91 · see citing works
Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration
Kuszczyk, M. A., Sanchez, S., Pankiewicz, J., Kim, J., Duszczyk, M., Guridi, M., Asuni, A. A., Sullivan, P. M., Holtzman, D. M., & Sadowski, M. J. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.01.034 · Cited by 89 · see citing works
β‐Amyloid Peptides Increase the Binding and Internalization of Apolipoprotein E to Hippocampal Neurons
Beffert, U., Aumont, N., Dea, D., Lussier‐Cacan, S., Davignon, J., & Poirier, J. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70041458.x · Cited by 77 · see citing works
Membrane Localization of β-Amyloid 1–42 in Lysosomes
Liu, R., Zhou, Q., Ji, S., Zhou, Q., Feng, D., Wu, Y., & Sui, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.036798 · Cited by 64 · see citing works
Significance of intracellular A beta 42 accumulation in Alzheimer s disease
Tabira, T. (2002) · Frontiers in bioscience · doi:10.2741/tabira · Cited by 60 · see citing works
Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer’s disease and apoE TR mouse cortex
Arold, S. P., Sullivan, P. M., Bilousova, T. V., Teng, E., Miller, C. A., Poon, W. W., Vinters, H. V., Cornwell, L. B., Saing, T., Cole, G. M., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0892-1 · Cited by 57 · see citing works
β-Amyloid1–42 Gene Transfer Model Exhibits Intraneuronal Amyloid, Gliosis, Tau Phosphorylation, and Neuronal Loss
Rebeck, G. W., Hoe, H., & Moussa, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.083915 · Cited by 54 · see citing works
Self-citation
Amyloid β-peptide levels in laser capture microdissected cornu ammonis 1 pyramidal neurons of Alzheimer's brain
Aoki, M., Volkmann, I., Tjernberg, L. O., Winblad, B., & Bogdanovic, N. (2008) · NeuroReport · doi:10.1097/wnr.0b013e328302c858 · Cited by 53 · see citing works
Scavenger receptor class B type I localizes to a late endosomal compartment
Ahras, M., Naing, T., & McPherson, R. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800055-jlr200 · Cited by 37 · see citing works
Intraneuronal ApoE in Human Visual Cortical Areas Reflects the Staging of Alzheimer Disease Pathology
Einstein, G., Patel, V., BAUTISTA, P., KENNA, M., MELONE, L., FADER, R., KARSON, K., MANN, S., Saunders, A. M., Hulette, C., et al. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199812000-00011 · Cited by 17 · see citing works
Untitled work
Cole (2000) · doi:10.1002/1097-0029(20000815)50:4

Flagged first, then by citations

Sorted by citations

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Apolipoprotein 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
Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities
Hemonnot, A.-L., Hua, J., Ulmann, L., & Hirbec, H. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00233 · Cited by 298 · see citing works
APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases
Fernández-Calle, R., Konings, S. C., Frontiñán-Rubio, J., García-Revilla, J., Camprubí-Ferrer, L., Svensson, M., Martinson, I., Boza-Serrano, A., Venero, J. L., Nielsen, H. M., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00566-4 · Cited by 278 · see citing works
Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities
Dorostkar, M. M., Zou, C., Blazquez-Llorca, L., & Herms, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1449-5 · Cited by 235 · see citing works
Dendritic Spine Pathology in Neurodegenerative Diseases
Herms, J., & Dorostkar, M. M. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044216 · Cited by 201 · see citing works
Dual roles for autophagy: Degradation and secretion of Alzheimer's disease Aβ peptide
Nilsson, P., & Saido, T. C. (2014) · BioEssays · doi:10.1002/bies.201400002 · Cited by 202 · see citing works
Resveratrol alleviates MPTP‐induced motor impairments and pathological changes by autophagic degradation of α‐synuclein via SIRT1‐deacetylated LC3
Guo, Y., Dong, S., Xin-Xin, C., Feng, Y., Liu, T., Yin, M., Kuo, S., Tan, E., Zhao, W., & Wu, Y. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600111 · Cited by 190 · see citing works
Self-citation
More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration
Lane-Donovan, C., Philips, G. T., & Herz, J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.005 · Cited by 158 · see citing works
The Beta Amyloid Dysfunction (BAD) Hypothesis for Alzheimer’s Disease
Hillen, H. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01154 · Cited by 106 · see citing works
Autophagy-Related Protein 7 Deficiency in Amyloid β (Aβ) Precursor Protein Transgenic Mice Decreases Aβ in the Multivesicular Bodies and Induces Aβ Accumulation in the Golgi
Nilsson, P., Sekiguchi, M., Akagi, T., Izumi, S., Komori, T., Hui, K. K., Sörgjerd, K. M., Tanaka, M., Saito, T., Iwata, N., et al. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.10.011 · Cited by 100 · see citing works
Multi-omic comparison of Alzheimer’s variants in human ESC–derived microglia reveals convergence at APOE
Liu, T., Zhu, B., Liu, Y., Zhang, X., Yin, J., Li, X., Jiang, L.-L., Hodges, A. P., Rosenthal, S. B., Zhou, L., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200474 · Cited by 69 · see citing works
Human Central Nervous System (CNS) ApoE Isoforms Are Increased by Age, Differentially Altered by Amyloidosis, and Relative Amounts Reversed in the CNS Compared with Plasma
Baker-Nigh, A. T., Mawuenyega, K. G., Bollinger, J. G., Ovod, V., Kasten, T., Franklin, E. E., Liao, F., Jiang, H., Holtzman, D., Cairns, N. J., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.721779 · Cited by 54 · see citing works
CD200-, CX3CL1-, and TREM2-mediated neuron-microglia interactions and their involvements in Alzheimer’s disease
Zhang, L., Xu, J., Gao, J., Wu, Y., Yin, M., & Zhao, W. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0084 · Cited by 48 · see citing works
Self-citation
The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer’s disease
Collins, J. M., King, A. E., Woodhouse, A., Kirkcaldie, M. T. K., & Vickers, J. C. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.02.034 · Cited by 43 · see citing works
The Interplay Between Apolipoprotein E4 and the Autophagic–Endocytic–Lysosomal Axis
Schmukler, E., Michaelson, D. M., & Pinkas-Kramarski, R. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0892-4 · Cited by 35 · see citing works
REMOVED: Nanowired delivery of cerebrolysin with neprilysin and p-Tau antibodies induces superior neuroprotection in Alzheimer's disease
Sharma, H. S., Muresanu, D. F., Nozari, A., Lafuente, J. V., Tian, Z. R., Ozkızılcık, A., Manzhulo, I., Mössler, H., & Sharma, A. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.03.009 · Cited by 33 · see citing works
Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4
Argyri, L., Dafnis, I., Theodossiou, T. A., Gantz, D., Stratikos, E., & Chroni, A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.538124 · Cited by 30 · see citing works
Mitogen-activated protein kinase signaling pathways promote low-density lipoprotein receptor-related protein 1-mediated internalization of beta-amyloid protein in primary cortical neurons
Yang, W., Ma, K., Qian, Y., Zhang, J.-S., Feng, G.-F., Shi, L., Zhang, Z., & Liu, Z. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.04.013 · Cited by 27 · see citing works
Aging reduces glial uptake and promotes extracellular accumulation of Aβ from a lentiviral vector
Zhao, W., Zhang, J., Davis, E. G., & Rebeck, G. W. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00210 · Cited by 25 · see citing works
Self-citation
Lower functional connectivity of default mode network in cognitively normal young adults with mutation of APP, presenilins and APOE ε4
Su, Y. Y., Zhang, X. D., Schoepf, U. J., Varga‐Szemes, Á., Stubenrauch, A. C., Liang, X., Zheng, L. J., Zheng, G., Kong, X., Xu, Q., et al. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-016-9556-z · Cited by 25 · see citing works
Decreased immunoglobulin G in brain regions of elder female APOE4-TR mice accompany with Aβ accumulation
Zhang, L., Xu, J., Gao, J., Chen, P., Yin, M., & Zhao, W. (2019) · Immunity & Ageing · doi:10.1186/s12979-018-0142-7 · Cited by 20 · see citing works
Self-citation
Apolipoprotein E intersects with amyloid-β within neurons
Konings, S. C., Nyberg, E., Martinsson, I., Torres-Garcia, L., Klementieva, O. L., Almeida, C. G., & Gouras, G. K. (2023) · Life Science Alliance · doi:10.26508/lsa.202201887 · Cited by 12 · see citing works
Development of AD-Like Pathology in Skeletal Muscle
Chen, X., Miller, N. M., Afghah, Z., & Geiger, J. D. (2019) · Journal of Parkinson’s Disease and Alzheimer’s Disease · doi:10.13188/2376-922x.1000028 · Cited by 10 · see citing works
APOE Genotype Alters Immunoglobulin Subtypes in Knock-In Mice
Zhou, Y., Zhao, W., Al‐Muhtasib, N., & Rebeck, G. W. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142184 · Cited by 9 · see citing works
Self-citation
Altered Cholesterol Intracellular Trafficking and the Development of Pathological Hallmarks of Sporadic AD
Chen, X., Liang, H., Soliman, M. L., & Geiger, J. D. (2014) · Journal of Parkinson’s Disease and Alzheimer’s Disease · doi:10.13188/2376-922x.1000002 · Cited by 7 · see citing works
An Insight into Medicinal Chemistry and SAR Studies of Cholinesterase and BACE-1 Inhibitors for Alzheimer's Disease
Shome, A., Jha, K. T., Chahat, Chawla, V., & Chawla, P. A. (2024) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273315191241002115155 · Cited by 4 · see citing works
Blood Markers in Healthy-Aged Nonagenarians: A Combination of High Telomere Length and Low Amyloidβ Are Strongly Associated With Healthy Aging in the Oldest Old
Fernández‐Eulate, G., Alberro, A., Muñoz‐Culla, M., Zulaica, M., Zufiría, M., Barandiarán, M., Etxeberría, I., Yanguas, J. J., Gallardo, M. M., Soberón, N. E., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00380 · Cited by 3 · see citing works
Interaction of Two Amphipathic α-Helix Bundle Proteins, ApoLp-III and ApoE 3, with the Oil–Aqueous Interface
Mirheydari, M., Putta, P., Mann, E. K., & Kooijman, E. E. (2021) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.1c00271 · Cited by 3 · see citing works
Faculty Opinions recommendation of The beta amyloid dysfunction (BAD) hypothesis for alzheimer's disease.
Duffin, J. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736901473.793567387
Neuronal age drives β-sheet accumulation and, together with ApoE4, enhances synaptic Aβ localization in APP NL-F neuronsPreprint
Konings, S. C., Nyberg, E., Martinsson, I., Thakore, R., Gouras, G. K., & Klementieva, O. L. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.10.697647
Implication de nouvelles cibles microgliales, Cst7 et Clec7a/Dectin-1, dans le développement et la progression de la maladie d'Alzheimer
Hemonnot-Girard, A.-L. (2021) · theses.fr (ABES) · doi:10.70675/9c8a4775zd774z494ez9bbazf7566faefa8f

Aging reduces glial uptake and promotes extracellular accumulation of Aβ from a lentiviral vector
Zhao, W., Zhang, J., Davis, E. G., & Rebeck, G. W. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00210 · Cited by 25 · see citing works
Self-citation
Gene delivery of human apolipoprotein E alters brain Aβ burden in a mouse model of Alzheimer's disease
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
P3–209: ApoE4 induces Aβ mediated apoptosis in vivo
Belinson, H., & Michaelson, D. M. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.05.1478
β-Amyloid1–42 Gene Transfer Model Exhibits Intraneuronal Amyloid, Gliosis, Tau Phosphorylation, and Neuronal Loss
Rebeck, G. W., Hoe, H., & Moussa, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.083915 · Cited by 54 · see citing works
Self-citation
Gene Transfer of Human <i>Apoe</i> Isoforms Results in Differential Modulation of Amyloid Deposition and Neurotoxicity in Mouse Brain
Hudry, E., Dashkoff, J., Roe, A. D., Takeda, S., Koffie, R. M., Hashimoto, T., Scheel, M., Spires-Jones, T., Arbel-Ornath, M., Betensky, R., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007000 · Cited by 187 · see citing works

Authors: Zhao, W., Dumanis, S. B., Tamboli, I. Y., Rodriguez, G. A., Jo LaDu, M., Moussa, C. E. H., & William Rebeck, G.
Affiliations: Shanghai Jiao Tong University (CN)
Georgetown University Medical Center (US)
ORCID: Dumanis, S. B.
Rodriguez, G. A.
Moussa, C. E. H.
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 2013-10-23
Volume: 23
Issue: 5
Pages: 1365-1375
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/ddt525
PMC: PMC3919009
OpenAlex: W2170589861
Cited by: 32
References: 61
Citations by year: 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 6 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 6
FWCI: 3.24
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Human Molecular Genetics (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Georgetown University
China Scholarship Council
National Institutes of Health (IA 52242)
National Institute on Aging (P01AG030128, R01AG035379)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: apolipoprotein E, APOE ε4, amyloid-beta 42, Alzheimer's disease, lentiviral transduction, targeted replacement mice, tau phosphorylation, neuronal cell death, microglia, astrocytes
MeSH terms: Animals, Cerebral Cortex, Genetic Vectors, Genotype, Humans, Mice, Transgenic, Microinjections, Neurons, Protein Binding, Transduction, Genetic, Gene Expression, Lentivirus, Amyloid beta-Peptides, Microglia, Gene Transfer Techniques, Protein Transport, Intracellular Space, Mice, Apolipoprotein E4

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Human APOE genotype affects intraneuronal A 1-42 accumulation in a lentiviral gene transfer model

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks