ApoE4 Decreases Spine Density and Dendritic Complexity in Cortical Neurons In Vivo
Open accessAbstract
The three human alleles of apolipoprotein E (APOE) differentially influence outcome after CNS injury and affect one's risk of developing Alzheimer's disease (AD). It remains unclear how ApoE isoforms contribute to various AD-related pathological changes (e.g., amyloid plaques and synaptic and neuron loss). Here, we systematically examined whether apoE isoforms (E2, E3, E4) exhibit differential effects on dendritic spine density and morphology in APOE targeted replacement (TR) mice, which lack AD pathological changes. Using Golgi staining, we found age-dependent effects of APOE4 on spine density in the cortex. The APOE4 TR mice had significantly reduced spine density at three independent time points (4 weeks, 3 months, and 1 year, 27.7% ± 7.4%, 24.4% ± 8.6%, and 55.6% ± 10.5%, respectively) compared with APOE3 TR mice and APOE2 TR mice. Additionally, in APOE4 TR mice, shorter spines were evident compared with other APOE TR mice at 1 year. APOE2 TR mice exhibited longer spines as well as significantly increased apical dendritic arborization in the cortex compared with APOE4 and APOE3 TR mice at 4 weeks. However, there were no differences in spine density across APOE genotypes in hippocampus. These findings demonstrate that apoE isoforms differentially affect dendritic complexity and spine formation, suggesting a role for APOE genotypes not only in acute and chronic brain injuries including AD, but also in normal brain functions.
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The presence of any human apoE isoform led to increased spine number at 3 months of age in comparison to mice that lack apoE.
“They compared dendritic spine number and length between neurons from mice lacking apoE altogether and mice in which a human APOE isoform replaced the mouse APOE gene, and demonstrated that the presence of any human apoE isoform led to increased spine number at 3 months of age in comparison to mice that lack apoE [Dumanis et al. (2009), their Fig.3A-C].”
From Differential Effects of ApoE Isoforms on Dendritic Spines<i>In Vivo</i>: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations (2010) · cites this paper as Dumanis et al. (2009)
The Results section on 4-week-old mice (Fig. 1C–E; page not provided) reports greater cortical spine density in APOE2 and APOE3 replacement mice than in apoE-deficient mice, but says APOE4 mice had similarly reduced density to mice lacking apoE. The 3-month Results (Fig. 3A–C; page not provided) compare the three human isoforms with one another, not with apoE-deficient mice. Thus, the paper does not establish the claimed increase for every isoform at 3 months. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAt all ages examined, mice expressing APOE4 had significantly fewer dendritic spines in layer II/III cortical pyramidal neurons than mice expressing APOE2 or APOE3.
“One of the principal findings was that, at all ages examined, mice expressing APOE4 had significantly fewer dendritic spines in layer II/III cortical pyramidal neurons than mice expressing APOE2 or APOE3 [Dumanis et al. (2009), their Fig. 1, Fig. 3].”
From Differential Effects of ApoE Isoforms on Dendritic Spines<i>In Vivo</i>: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations (2010) · cites this paper as Dumanis et al. (2009)
The study by Dumanis et al. (2009) is the first to systematically compare dendritic spines in vivo in mice in which the human APOE2, APOE3, or APOE4 gene has been substituted into the mouse APOE locus.
“The study by Dumanis et al. (2009) is the first to systematically compare dendritic spines in vivo in mice in which the human APOE2, APOE3, or APOE4 gene has been substituted into the mouse APOE locus.”
From Differential Effects of ApoE Isoforms on Dendritic Spines<i>In Vivo</i>: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations (2010) · cites this paper as Dumanis et al. (2009)
Spine length differed between mice expressing different APOE isoforms.
“Dumanis et al. (2009) also found that spine length differed between mice expressing different APOE isoforms.”
From Differential Effects of ApoE Isoforms on Dendritic Spines<i>In Vivo</i>: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations (2010) · cites this paper as Dumanis et al. (2009)
In the 1-year-old cohort, the mice expressing the APOE4 gene had shorter spines than APOE2 and APOE3 mice.
“In the 1-year-old cohort, the mice expressing the APOE4 gene had shorter spines than APOE2 and APOE3 mice [Dumanis et al. (2009), their Fig.3H].”
From Differential Effects of ApoE Isoforms on Dendritic Spines<i>In Vivo</i>: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations (2010) · cites this paper as Dumanis et al. (2009)
At 1 month of age, APOE2 mice had longer cortical spines than APOE3 and APOE4 mice.
“At 1 month of age, APOE2 mice had longer cortical spines than APOE3 and APOE4 mice [Dumanis et al. (2009), their Fig. 1 F-H].”
From Differential Effects of ApoE Isoforms on Dendritic Spines<i>In Vivo</i>: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations (2010) · cites this paper as Dumanis et al. (2009)
No differences in cortical spine density between APOE2 and APOE3 mice were observed.
“No differences in cortical spine density between APOE2 and APOE3 mice were observed [Dumanis et al. (2009), their Fig. 1, Fig. 3].”
From Differential Effects of ApoE Isoforms on Dendritic Spines<i>In Vivo</i>: Linking an Alzheimer's Disease Risk Factor with Synaptic Alterations (2010) · cites this paper as Dumanis et al. (2009)
The absence of clear differences in pre- and post-synaptic proteins in this study does not rule out the possibility that structural synaptic changes observed by others are present.
“This, however, does not rule out the possibility the structural synaptic changes might be present that have been observed by others (Dumanis et al., 2009).”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Dumanis et al., 2009
There is an association between the apoE4 and spine deficits in vivo.
“Other previous studies also reported an association between the apoE4 and spine deficits in vivo (Basak and Kim, 2010; Dumanis et al., 2009; Ji et al., 2003; Wang et al., 2005).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Dumanis et al., 2009
Apolipoprotein E4 decreases spine density both in vivo and in vitro.
“apolipoprotein (apo) E4–a major genetic risk factor for Alzheimer's disease–decreases spine density both in vivo [18], [19] and in vitro [20], [21]”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [18]
Human APOE ε4 reduces dendritic length and branching in the mouse cortex and hippocampus.
“In another study, human APOE ε4 was found to reduce dendritic length and branching in the mouse cortex and hippocampus67.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [67]
ApoE4 impairs synaptogenesis and decreases dendritic spine density in vivo and in vitro in primary neuronal cultures.
“ApoE4 impairs synaptogenesis and decreases dendritic spine density in vivo and in vitro in primary neuronal cultures [72, 73].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [73]
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Cites
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
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376 · see citing works
CNS synaptogenesis promoted by glia-derived cholesterol
Mauch, D. H., Nägler, K., Schumacher, S., Göritz, C., Müller, E.-C., Otto, A., & Pfrieger, F. W. (2001) · Science · doi:10.1126/science.294.5545.1354 · Cited by 1,711 · see citing works
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 polymorphism and Alzheimer's disease
Poirier, J., Bertrand, P., Poirier, J., Kogan, S., Gauthier, S., Poirier, J., Gauthier, S., Davignon, J., Bouthillier, D., & Davignon, J. (1993) · The Lancet · doi:10.1016/0140-6736(93)91705-q · Cited by 1,108 · 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
Self-citationDifferential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795 · see citing works
Association of apolipoprotein E polymorphism with outcome after head injury
Teasdale, G. M., Nicoll, J. A. R., Murray, G. D., & Fiddes, M. (1997) · The Lancet · doi:10.1016/s0140-6736(97)04318-3 · Cited by 683 · 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
Regulation of Dendritic Spine Morphology by SPAR, a PSD-95-Associated RapGAP
Pak, D. T. S., Yang, S., Rudolph-Correia, S., Kim, E., & Sheng, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00355-5 · Cited by 385 · 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 361 · 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
Bellosta, S., Nathan, B. P., Orth, M., Dong, L.-M., Mahley, R. W., & Pitas, R. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.27063 · Cited by 313 · see citing works
[Apolipoprotein E polymorphism and Alzheimer disease].
van der Weide, J., Steijns, L. S. W., Jl, T., Wj, N., & Klaverwijden, G. (1996) · PubMed · Cited by 297 · 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
Apolipoprotein E receptors: linking brain development and alzheimer's disease
Herz, J., & Beffert, U. (2000) · Nature reviews. Neuroscience · doi:10.1038/35036221 · Cited by 219 · see citing works
Interaction of Reelin with Amyloid Precursor Protein Promotes Neurite Outgrowth
Hoe, H.-S., Lee, K. J., Carney, R. S. E., Lee, J., Markova, A., Lee, J.-Y., Howell, B. W., Hyman, B. T., Pak, D. T. S., Bu, G., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4872-08.2009 · Cited by 219 · see citing works
Self-citationJi, Y., Gong, Y., Gan, W., Beach, T., Holtzman, D. M., & Wisniewski, T. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.08.007 · Cited by 189 · see citing works
Apolipoprotein E ϵ4 allele and hippocampal volume in twins with normal cognition
Plassman, B. L., Welsh-Bohmer, K. A., Bigler, E. D., Johnson, S. C., Anderson, C. V., Helms, M. J., Saunders, A. M., & Breitner, J. C. S. (1997) · Neurology · doi:10.1212/wnl.48.4.985 · Cited by 145 · see citing works
Human apoE4-targeted replacement mice display synaptic deficits in the absence of neuropathology.
Wang, C., Wilson, W. A., Moore, S. D., Mace, B. E., Maeda, N., Schmechel, D. E., & Sullivan, P. M. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.10.013 · Cited by 138 · 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
APOE related alterations in cerebral activation even at college age
Scarmeas, N. (2005) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.053645 · Cited by 97 · see citing works
del R�o, M. R., & DeFelipe, J. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960603)369:3 · Cited by 97 · see citing works
ApoE 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-citationTeter, B., Xu, P. ‐., Gilbert, J. R., Roses, A. D., Galasko, D., & Cole, G. M. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0732613.x · Cited by 88 · see citing works
Brodbeck, J., Balestra, M. E., Saunders, A. M., Roses, A. D., Mahley, R. W., & Huang, Y. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709906104 · Cited by 86 · see citing works
Yoshizawa, T., Yamakawa‐Kobayashi, K., Komatsuzaki, Y., Arinami, T., Oguni, E., Mizusawa, H., Shoji, S., & Hamaguchi, H. (1994) · Annals of Neurology · doi:10.1002/ana.410360416 · Cited by 71 · see citing works
Alpár, A., Ueberham, U., Brückner, M. K., Seeger, G., Arendt, T., & Gärtner, U. (2006) · Brain Research · doi:10.1016/j.brainres.2006.04.109 · Cited by 67 · see citing works
Qiu, S., Korwek, K. M., & Weeber, E. J. (2005) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2005.08.009 · Cited by 61 · see citing works
Self-citationAPOE ε2/ε4 Genotype a Risk Factor for Primary Progressive Aphasia in Women
Daniele, A., Matera, M. G., Seripa, D., Acciarri, A., Bizzarro, A., Pilotto, A., & Masullo, C. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.136 · Cited by 10 · see citing works
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Cited by
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Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396 · 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
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758 · see citing works
Dendritic spine pathology in neuropsychiatric disorders
Penzes, P., Cahill, M. E., Jones, K. A., VanLeeuwen, J.-E., & Woolfrey, K. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2741 · Cited by 1,523 · see citing works
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
Apolipoprotein 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
The Neuropathology and Neurobiology of Traumatic Brain Injury
Blennow, K., Hardy, J., & Zetterberg, H. (2012) · Neuron · doi:10.1016/j.neuron.2012.11.021 · Cited by 669 · see citing works
Dendritic Spines: The Locus of Structural and Functional Plasticity
Sala, C., & Segal, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00012.2013 · Cited by 465 · see citing works
ApoE4: an emerging therapeutic target for Alzheimer’s disease
Safieh, M., Korczyn, A. D., & Michaelson, D. M. (2019) · BMC Medicine · doi:10.1186/s12916-019-1299-4 · Cited by 449 · see citing works
Targa Dias Anastacio, H., Matosin, N., & Ooi, L. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02024-7 · Cited by 401 · see citing works
Apolipoprotein E in Alzheimer's Disease: An Update
Yu, J.-T., Tan, L., & Hardy, J. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014300 · Cited by 394 · see citing works
ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108572 · Cited by 379 · 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
Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
Henstridge, C. M., Hyman, B. T., & Spires-Jones, T. L. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0113-1 · Cited by 348 · 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
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
Ungar, L., Altmann, A., & Greicius, M. D. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9272-x · Cited by 248 · see citing works
Achariyar, T. M., Li, B., Peng, W., Verghese, P. B., Shi, Y., McConnell, E., Benraiss, A., Kasper, T., Song, W., Takano, T., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0138-8 · Cited by 250 · see citing works
Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes
Chung, W.-S., Verghese, P. B., Chakraborty, C., Joung, J., Hyman, B. T., Ulrich, J. D., Holtzman, D. M., & Barres, B. A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609896113 · Cited by 242 · see citing works
APOE genotype alters glial activation and loss of synaptic markers in mice
Zhu, Y., Nwabuisi‐Heath, E., Dumanis, S. B., Tai, L. M., Yu, C., Rebeck, G. W., & Ladu, M. J. (2012) · Glia · doi:10.1002/glia.22289 · Cited by 224 · see citing works
Self-citationKim, J., Jiang, H., Park, S., Eltorai, A. E. M., Stewart, F. R., Yoon, H., Basak, J. M., Finn, M. B., & Holtzman, D. M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3773-11.2011 · Cited by 199 · see citing works
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183 · see citing works
Reduced Hippocampal Volume in Healthy Young ApoE4 Carriers: An MRI Study
O’Dwyer, L., Lamberton, F., Matura, S., Tanner, C. J., Scheibe, M., Miller, J., Rujescu, D., Prvulovic, D., & Hampel, H. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048895 · Cited by 190 · see citing works
The Role of APOE and TREM2 in Alzheimer′s Disease—Current Understanding and Perspectives
Wolfe, C. M., Fitz, N. F., Nam, K. N., Lefterov, I. M., & Koldamova, R. P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010081 · Cited by 192 · see citing works
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
Alzheimer's Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function
Battista, A. M. D., Heinsinger, N. M., & Rebeck, G. W. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160401115127 · Cited by 184 · see citing works
Self-citationSuri, S., Heise, V., Trachtenberg, A. J., & Mackay, C. E. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.10.010 · Cited by 183 · see citing works
Borovac, J., Bosch, M., & Okamoto, K. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.07.001 · Cited by 180 · see citing works
APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: A review
O'Donoghue, M. C., Murphy, S. E., Zamboni, G., Nobre, A. C., & Mackay, C. E. (2018) · Cortex · doi:10.1016/j.cortex.2018.03.025 · Cited by 176 · see citing works
Aβ-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's disease
Huang, Y. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.04.004 · Cited by 170 · see citing works
Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease
Williams, T., Borchelt, D., & Chakrabarty, P. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-0358-9 · Cited by 166 · see citing works
Apolipoprotein E, not fibrillar β-amyloid, reduces cerebral glucose metabolism in normal aging
Jagust, W. J., Landau, S. M., & Initiative, F. T. A. D. N. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3266-12.2012 · Cited by 162 · see citing works
Yamazaki, Y., Painter, M. M., Bu, G., & Kanekiyo, T. (2016) · CNS Drugs · doi:10.1007/s40263-016-0361-4 · Cited by 166 · see citing works
The role of APOE on lipid homeostasis and inflammation in normal brains
Rebeck, G. W. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075408 · Cited by 160 · see citing works
Self-citationAstrocytic ApoE reprograms neuronal cholesterol metabolism and histone-acetylation-mediated memory
Li, X., Zhang, J., Li, D., He, C., He, K., Xue, T., Wan, L., Zhang, C., & Liu, Q. (2021) · Neuron · doi:10.1016/j.neuron.2021.01.005 · Cited by 165 · see citing works
Flowers, S. A., & Rebeck, G. W. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104724 · Cited by 149 · see citing works
Self-citationTzioras, M., Davies, C., Newman, A., Jackson, R., & Spires‐Jones, T. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12529 · Cited by 147 · see citing works
Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in alzheimer disease
Wadhwani, A. R., Affaneh, A., Van Gulden, S., & Kessler, J. A. (2019) · Annals of Neurology · doi:10.1002/ana.25455 · Cited by 142 · 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
“Other previous studies also reported an association between the apoE4 and spine deficits in vivo (Basak and Kim, 2010; Dumanis et al., 2009; Ji et al., 2003; Wang et al., 2005).”
BackgroundResultRodriguez, G. A., Burns, M. P., Weeber, E. J., & Rebeck, G. W. (2013) · Learning & Memory · doi:10.1101/lm.030031.112 · Cited by 134 · see citing works
Self-citationLow-doses of cisplatin injure hippocampal synapses: A mechanism for ‘chemo’ brain?
Andres, A. L., Gong, X. W., Di, K., & Bota, D. A. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.02.020 · Cited by 132 · see citing works
The effects of APOE on the functional architecture of the resting brain
Trachtenberg, A. J., Filippini, N., Ebmeier, K. P., Smith, S. M., Karpe, F., & Mackay, C. E. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.07.059 · Cited by 129 · see citing works
Chronic neurodegenerative consequences of traumatic brain injury
Chauhan, N. B. (2014) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-130354 · Cited by 126 · see citing works
The Early Events That Initiate β-Amyloid Aggregation in Alzheimer’s Disease
Zhang, X., Fu, Z., Meng, L., He, M., & Zhang, Z. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00359 · Cited by 122 · see citing works
The dendritic hypothesis for Alzheimer's disease pathophysiology
Cochran, J. N., Hall, A. M., & Roberson, E. D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.004 · Cited by 114 · see citing works
Liraz, O., Boehm-Cagan, A., & Michaelson, D. M. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-16 · Cited by 118 · see citing works
Synaptic Elimination in Neurological Disorders
Cardozo, P. L., de Lima, I. B. Q., Maciel, E. M. A., Silva, N. C., Dobránsky, T., & Ribeiro, F. M. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666190603170511 · Cited by 113 · see citing works
Impaired regulation of synaptic actin cytoskeleton in Alzheimer's disease
Penzes, P., & VanLeeuwen, J. (2011) · Brain Research Reviews · doi:10.1016/j.brainresrev.2011.01.003 · Cited by 113 · see citing works
Chang, L.-H., Andres, M., Sadino, J., Jiang, C. S., Nakama, H., Miller, E. N., & Ernst, T. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.07.010 · Cited by 113 · see citing works
Keene, C. D., Cudaback, E., Li, X., Montine, K. S., & Montine, T. J. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.08.002 · Cited by 103 · see citing works
Brodbeck, J., McGuire, J., Liu, Z., Meyer-Franke, A., Balestra, M. E., Jeong, D.-E., Pleiss, M., McComas, C., Hess, F., Witter, D., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.217380 · Cited by 113 · 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-citationLitvinchuk, A., Huynh, T. V., Shi, Y., Jackson, R. J., Finn, M. B., Manis, M., Francis, C. M., Tran, A. C., Sullivan, P. M., Ulrich, J. D., et al. (2021) · Annals of Neurology · doi:10.1002/ana.26043 · Cited by 91 · see citing works
Lipoproteins in the Central Nervous System: From Biology to Pathobiology
Raulin, A.-C., Martens, Y. A., & Bu, G. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104801 · Cited by 89 · see citing works
Mattsson, N., Groot, C., Jansen, W. J., Landau, S. M., Villemagne, V. L., Engelborghs, S., Mintun, M. M., Lleo, A., Molinuevo, J. L., Jagust, W. J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.009 · Cited by 88 · see citing works
Dendritic Spines: Mediators of Cognitive Resilience in Aging and Alzheimer’s Disease
Walker, C. K., & Herskowitz, J. H. (2021) · The Neuroscientist · doi:10.1177/1073858420945964 · Cited by 86 · see citing works
Mechanisms linking apolipoprotein E isoforms with cardiovascular and neurological diseases.
Huang, Y. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32833af368 · Cited by 82 · see citing works
A “multi-omics” analysis of blood–brain barrier and synaptic dysfunction in <i>APOE4</i> mice
Barisano, G., Kisler, K., Wilkinson, B., Nikolakopoulou, A. M., Sagare, A. P., Wang, Y., Gilliam, W., Huuskonen, M. T., Hung, S.-T., Ichida, J. K., et al. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20221137 · Cited by 78 · see citing works
APOE and neuroenergetics: an emerging paradigm in Alzheimer's disease
Wolf, A. B., Caselli, R. J., Reiman, E. M., & Valla, J. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.10.011 · Cited by 79 · see citing works
Presence of ApoE ε4 Allele Associated with Thinner Frontal Cortex in Middle Age
Fennema‐Notestine, C., Panizzon, M. S., Thompson, W., Chen, C., Eyler, L. T., Fischl, B. R., Franz, C. E., Grant, M. D., Jak, A. J., Jernigan, T. L., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-0002 · Cited by 76 · see citing works
Perkins, M., Wolf, A. B., Chavira, B., Shonebarger, D., Meckel, J. P., Leung, L., Ballina, L. E., Ly, S., Saini, A., Jones, T. B., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151205 · Cited by 74 · see citing works
Endoplasmic reticulum calcium stores in dendritic spines
Segal, M., & Korkotian, E. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00064 · Cited by 73 · see citing works
Lewandowski, C. T., Maldonado Weng, J., & LaDu, M. J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104811 · Cited by 72 · see citing works
Self-citationSen, A., Alkon, D. L., & Nelson, T. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.312710 · Cited by 69 · see citing works
Animal models of chemotherapy-induced cognitive decline in preclinical drug development
John, J., Kinra, M., Mudgal, J., Viswanatha, G. L., & Nandakumar, K. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05977-7 · Cited by 69 · see citing works
Hippocampal Volume Differences Between Healthy Young Apolipoprotein E ε2 and ε4 Carriers
Alexopoulos, P., Richter‐Schmidinger, T., Horn, M., Maus, S., Reichel, M., Sidiropoulos, C., Rhein, C., Lewczuk, P., Doerfler, A., & Kornhuber, J. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110356 · Cited by 69 · see citing works
Klein, 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
Intracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer’s Disease
Perdigão, C., Barata, M. A., Araújo, M. N. C. D. F., Mirfakhar, F. S., Castanheira, J., & Almeida, C. G. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00072 · Cited by 63 · see citing works
Bexarotene-Activated Retinoid X Receptors Regulate Neuronal Differentiation and Dendritic Complexity
Mounier, A., Georgiev, D., Nam, K. N., Fitz, N. F., Castranio, E. L., Wolfe, C. M., Cronican, A. A., Schug, J., Lefterov, I., & Koldamova, R. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1001-15.2015 · Cited by 64 · see citing works
Transcriptional Effects of ApoE4: Relevance to Alzheimer’s Disease
Theendakara, V., Peters-Libeu, C. A., Bredesen, D. E., & Rao, R. V. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0757-2 · Cited by 63 · see citing works
The dark sides of amyloid in Alzheimer's disease pathogenesis
Sorrentino, P., Iuliano, A., Polverino, A., Jacini, F., & Sorrentino, G. (2014) · FEBS Letters · doi:10.1016/j.febslet.2013.12.038 · Cited by 64 · see citing works
<i>APOE</i> ε2ε4 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults
Oveisgharan, S., Buchman, A. S., Yu, L., Farfel, J., Hachinski, V., Gaiteri, C., De Jager, P. L., Schneider, J. A., & Bennett, D. A. (2018) · Neurology · doi:10.1212/wnl.0000000000005677 · Cited by 62 · see citing works
Fernandez, H. R., Varma, A., Flowers, S. A., & Rebeck, G. W. (2020) · Cancers · doi:10.3390/cancers12123842 · Cited by 62 · see citing works
Self-citationThe effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease
Trachtenberg, A. J., Filippini, N., Cheeseman, J., Duff, E. P., Neville, M. J., Ebmeier, K. P., Karpe, F., & Mackay, C. E. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.11.011 · Cited by 59 · see citing works
Smith, J. C., Lancaster, M. A., Nielson, K. A., Woodard, J. L., Seidenberg, M., Durgerian, S., Sakaie, K., & Rao, S. M. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.08.007 · Cited by 57 · see citing works
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
Zhu, C., Xu, B., Sun, X., Zhu, Q., & Sui, Y. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0269-5 · Cited by 55 · 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
Self-citationApolipoprotein E as a β-amyloid-independent factor in Alzheimer’s disease
Wolf, A. B., Valla, J., Bu, G., Kim, J., LaDu, M., Reiman, E. M., & Caselli, R. J. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt204 · Cited by 55 · see citing works
Self-citationOlde Loohuis, N. F. M., Kole, K., Glennon, J. C., Karel, P., Van der Borg, G., Van Gemert, Y., Van den Bosch, D., Meinhardt, J., Kos, A., Shahabipour, F., et al. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.05.006 · Cited by 54 · see citing works
Introducing Human <i>APOE</i> into A<i>β</i> Transgenic Mouse Models
Tai, L. M., Youmans, K. L., Jungbauer, L., Yu, C., & LaDu, M. J. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/810981 · Cited by 52 · see citing works
Self-citationDifferential splicing and glycosylation of Apoer2 alters synaptic plasticity and fear learning
Wasser, C. R., Masiulis, I., Durakoglugil, M. S., Lane-Donovan, C., Xian, X., Beffert, U., Agarwala, A., Hammer, R. E., & Herz, J. (2014) · Science Signaling · doi:10.1126/scisignal.2005438 · Cited by 48 · see citing works
NAKAI, T., Yamada, K., & Mizoguchi, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115549 · Cited by 52 · see citing works
ApoE receptor 2 regulates synapse and dendritic spine formation
Dumanis, S. B., Cha, H.-J., Song, J. M., Trotter, J. H., Spitzer, M., Lee, J.-Y., Weeber, E. J., Turner, R. S., Pak, D. T. S., Rebeck, G. W., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017203 · Cited by 45 · see citing works
Self-citationAllen, M., Ghosh, S., Ahern, G. P., Villapol, S., Maguire‐Zeiss, K. A., & Conant, K. E. (2016) · Scientific Reports · doi:10.1038/srep35497 · Cited by 49 · see citing works
The Synergistic Effects of APOE Genotype and Obesity on Alzheimer’s Disease Risk
Jones, N. S., & Rebeck, G. W. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010063 · Cited by 50 · see citing works
Self-citationHuang, Y. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390924 · Cited by 48 · see citing works
Astrocytic and neuronal apolipoprotein E isoforms differentially affect neuronal excitability
Konings, S. C., Torres-Garcia, L., Martinsson, I., & Gouras, G. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.734001 · Cited by 43 · see citing works
A multi‐hit hypothesis for an <i>APOE4</i> ‐dependent pathophysiological state
Steele, O. G., Stuart, A. C., Minkley, L., Shaw, K., Bonnar, O., Anderle, S., Penn, A. C., Rusted, J., Serpell, L., Hall, C., et al. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15685 · Cited by 44 · see citing works
Maioli, 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
Rapid Estradiol Modulation of Neuronal Connectivity and Its Implications for Disease
Srivastava, D. P., & Penzes, P. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00077 · Cited by 44 · see citing works
Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development
Jain, S., Yoon, S. Y., Zhu, L., Brodbeck, J., Dai, J., Walker, D., & Huang, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046340 · Cited by 43 · see citing works
Sun, G., He, Y., Ma, X. K., Li, S., Chen, D., Gao, M., Qiu, S., Yin, J., Shi, J., & Wu, J. (2017) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12720 · Cited by 42 · see citing works
Loizzo, S., Rimondini, R., Travaglione, S., Fabbri, A., Guidotti, M., Ferri, A., Campana, G., & Fiorentini, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065898 · Cited by 42 · see citing works
Jain, S., Yoon, S. Y., Leung, L., Knöferle, J., & Huang, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059478 · Cited by 39 · see citing works
The Role of Apolipoprotein E Isoforms in Alzheimer’s Disease
Roda, A. R., Montoliu‐Gaya, L., & Villegas, S. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180740 · Cited by 40 · see citing works
Transgenic animal models of neurodegeneration based on human genetic studies
Harvey, B. K., Richie, C. T., Hoffer, B. J., & Airavaara, M. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0476-6 · Cited by 38 · see citing works
Shi, L., Du, X., Zhou, H., Tao, C.-L., Liu, Y.-T., Meng, F., Wu, G., Xiong, Y., Xia, C., Wang, Y., et al. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145714000601 · Cited by 38 · see citing works
- Authors
- Dumanis, S. B., Tesoriero, J. A., Babus, L. W., Nguyen, M. T., Trotter, J. H., Ladu, M. J., Weeber, E. J., Turner, R. S., Xu, B., Rebeck, G. W., & Hoe, H.-S.
- Affiliations
- Georgetown University Medical Center (US)
- Georgetown University (US)
- University of South Florida (US)
- University of Illinois Chicago (US)
- Corresponding author
- Hoe, Hyang-Sook
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-12-02
- Volume
- 29
- Issue
- 48
- Pages
- 15317-15322
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2846754
- OpenAlex
- W2167047846
- Cited by
- 220
- References
- 31
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 15 · 2021: 16 · 2020: 18 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 17 · 2015: 7 · 2014: 19 · 2013: 18 · 2012: 15
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Georgetown University
- National Institutes of Health
- National Institute on Aging (R01AG026478, P01AG030128, R29AG014473, R03AG032330, R01AG014473, AG032330, AG026478, AG014473)
- National Institute of Neurological Disorders and Stroke (R01NS050596)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, APOE ε4, APOE isoforms, dendritic spine density, dendritic complexity, cortical neurons, hippocampus, Alzheimer's disease risk, synaptic plasticity
- MeSH terms
- Age Factors, Analysis of Variance, Animals, Cells, Cultured, Cerebral Cortex, Dendrites, Embryo, Mammalian, Hippocampus, Humans, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Silver Staining, Rats, Sprague-Dawley, Protein Isoforms, Dendritic Spines, Mice, Rats, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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