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Behavioral phenotyping of GFAP-ApoE3 and -ApoE4 transgenic mice: ApoE4 mice show profound working memory impairments in the absence of Alzheimer’s-like neuropathology.
Abstract
For the purpose of studying the potential neurobehavioral effects of different human apolipoprotein E (apoE) isoforms produced within the brain, transgenic (TG) mice were generated in which human apoE3 or apoE4 isoforms were under control of an astrocyte-specific, glial fibrillary acidic protein promoter and these TG mice were bred back to apoE knockout (KO) mice. Behavioral phenotypes of apoE3 and apoE4 TG mice were derived by conducting a longitudinal study in which apoE3 and apoE4 TG mice were compared with apoE KO and wild-type (WT) mice (all male) on several behavioral measures. Analysis of locomotor activity, "open-field" behaviors, acoustic startle/prepulse inhibition, and elevated plus maze data suggested that the apoE TG/KO groups were more "emotionally reactive" than WT mice, with apoE4 mice typically being the most reactive. The absence of performance differences among groups on the rotating holeboard and water navigation tasks suggested intact reference memory processing in apoE TG/KO mice. However, apoE4 mice were profoundly impaired on a working memory-based protocol in the radial arm maze (11-14 months). Nonassociative factors (sensorimotor capacities or emotionality differences) did not appear to confound interpretation of the learning/memory results. Western blot analysis revealed no alterations in the level of synaptic, neuronal, or glial markers in neocortex or hippocampus and histologic analysis revealed no evidence of Abeta deposition or neuritic plaques…
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“Hartman et al. also demonstrated that apoE4 mice were more severely impaired in working memory in a radial arm maze test (Hartman et al., 2001).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Hartman et al., 2001
In the citing paper
“and were more severely impaired in learning and memory (Hartman et al., 2001; Raber et al., 1998; Raber et al., 2000).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Hartman et al., 2001
In the citing paper
“Some studies show no significant cognitive impairments compared to either wild type or human apoE3 expressing mice (Raber et al., 1998, Grootendorst et al., 2005, Hartman et al., 2001, van Meer et al., 2007)”
From Apolipoprotein E–low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner (2014) · cites this paper as Hartman et al., 2001
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Cites
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
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
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
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
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
Self-citationLack 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
Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112130 · Cited by 829
Rodgers, R. J., & Johnson, N. J. (1995) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)00138-m · Cited by 793
Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins
Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., & Mahley, R. W. (1987) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(87)90295-5 · Cited by 693
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
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Klein, R. C., & Yakel, J. L. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.045 · Cited by 27
Basaure, P., Guardia-Escote, L., Cabré, M., Peris‐Sampedro, F., Sánchez-Santed, F., Domingo, J. L., & Colomina, M. T. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02387-9 · Cited by 26
Caliban's heritance and the genetics of neuronal aging
Teter, B., & Finch, C. E. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.08.005 · Cited by 26
Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
Rhea, E. M., Hansen, K. M., Pemberton, S., Torres, E. R. S., Holden, S. J., Raber, J., & Banks, W. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-98061-1 · Cited by 22
Levi, O., Dolev, I., Belinson, H., & Michaelson, D. M. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04810.x · Cited by 22
Development of a water-escape motivated version of the Stone T-maze for mice
Pistell, P. J., & Ingram, D. K. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.12.029 · Cited by 22
Reverte, I., Peris‐Sampedro, F., Basaure, P., Campa, L., Sunol, C. E., Moreno, M., Domingo, J. L., & Colomina, M. T. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4113-9 · Cited by 23
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Krogsaeter, E., McKetney, J., Valiente‐Banuet, L., Marquez, A., Willis, A., Cakir, Z., Stevenson, E. J., Jang, G. Μ., Rao, A. T., Li, E., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2576613 · Cited by 22
Kulkarni, P., Grant, S. E., Morrison, T. R., Cai, X., Iriah, S. C., Kristal, B. S., Honeycutt, J. A., Brenhouse, H. C., Hartner, J. C., Madularu, D., et al. (2020) · Brain Research · doi:10.1016/j.brainres.2020.147030 · Cited by 19
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Pistell, P. J., Spangler, E. L., Kelley-Bell, B., Miller, M. G., de Cabo, R., & Ingram, D. K. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.12.004 · Cited by 20
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Segev, Y., Livne, A., Mints, M., & Rosenblum, K. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00170 · Cited by 18
Santangelo, A., Trinchese, F., & Arancio, O. (2003) · Neurochemical Research · doi:10.1023/a:1023251005197 · Cited by 18
Viggiano, A., Cacciola, G., Widmer, D. A. J., & Viggiano, D. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.05.032 · Cited by 17
Chaudhari, K., Wong, J. M., Vann, P. H., & Sumien, N. (2014) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2014.04.004 · Cited by 17
Martin, S. K., Gee, J. R., Bruce‐Keller, A. J., & Keller, J. N. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.10.085 · Cited by 17
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Jamal, M., Ameno, K., Miki, T., Tanaka, N., Ono, J., Shirakami, G., Sultana, R., Yu, N., & Kinoshita, H. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.02.006 · Cited by 16
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Parkison, S. A., Carlson, J. D., Chaudoin, T. R., Hoke, T. A., Schenk, A. K., Goulding, E. H., Pérez, L. C., & Bonasera, S. J. (2012) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2012.6346445 · Cited by 12
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Sultana, R., Ameno, K., Jamal, M., Miki, T., Tanaka, N., Ono, J., Kinoshita, H., & Nakamura, Y. (2012) · Neurological Sciences · doi:10.1007/s10072-012-1149-z · Cited by 9
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Hartman, R. E., Rojas, H. A., Tang, J., & Zhang, J. H. (2009) · Acta neurochirurgica. Supplementum · doi:10.1007/978-3-211-09469-3_25 · Cited by 10
Self-citationLee, B. H., Puri, T. A., & Galea, L. A. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819344-0.00010-7 · Cited by 8
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Zhu, J. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112904 · Cited by 6
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Yong, S. M., Ong, Q.-R., Siew, B. E., & Wong, B. (2014) · Food & Function · doi:10.1039/c4fo00428k · Cited by 1
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Hartman, R. E. (2012) · Springer protocols handbooks/Springer protocols · doi:10.1007/978-1-61779-576-3_15 · Cited by 1
Self-citationKoutseff, A. (2011) · OpenGrey (Institut de l'Information Scientifique et Technique)
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Thorndyke, & Earl, C. (2013)
Bouwer, S. (2010) · UWA Profiles and Research Repository (University of Western Australia)
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Liao, F., & Holtzman, D. M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802173-6.00010-1
Self-citationAlbrecht, M. A., & Foster, J. K. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3777-6_7
Sampedro, F. P. (2016) · TDX (Tesis Doctorals en Xarxa)
Jansen, D., Zerbi, V., Janssen, C. I. F., van Rooij, D., Dederen, P. J. W. C., Heerschap, A., & Broersen, L. M. (2013)
Lambert, J. (2006) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.30576.487883
Genetic Determinants of Human Longevity
Dato, S., Soerensen, M., & Rose, G. (2019) · MDPI eBooks · doi:10.3390/books978-3-03921-679-6
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Torres, E. R. S., & Raber, J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29090-9.00001-5
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Choi, C. Y., Venegas, J. J., Rauch, S. M., Walter, F. A., Ryan, J. N., Machireddy, M., Weisz, J. M., Tracy, G., Baker, A. J., Floresco, S., et al. (2026) · Physiology & Behavior · doi:10.1016/j.physbeh.2026.115308
Saul, A. (2013) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-3915
Metadata
- Authors
- Hartman, R. E., Wozniak, D. F., Nardi, A., Olney, J. W., Sartorius, L., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Wozniak, D.F.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 170
- Issue
- 2
- Pages
- 326-344
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2017595192
- Cited by
- 157
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 8 · 2019: 5 · 2018: 2 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 12 · 2012: 14
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG11355-06, AG13956, P01AG011355)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- apolipoprotein E, APOE ε4, APOE3, transgenic mice, GFAP promoter, astrocytes, working memory, reference memory, emotional reactivity, acoustic startle response, prepulse inhibition, radial maze, hippocampus, neocortex, Alzheimer's disease
- MeSH terms
- Acoustic Stimulation, Aging, Alzheimer Disease, Analysis of Variance, Animals, Apolipoproteins E, Cues, Emotions, Escape Reaction, Glial Fibrillary Acidic Protein, Humans, Learning, Male, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Phenotype, Promoter Regions, Genetic, Reaction Time, Space Perception, Reflex, Startle, Time Factors, Mice, Knockout, Mice, Apolipoprotein E3, Apolipoprotein E4
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