Behavioral phenotyping of GFAP-ApoE3 and -ApoE4 transgenic mice: ApoE4 mice show profound working memory impairments in the absence of Alzheimer’s-like neuropathology.

Hartman, R.E.; Wozniak, D.F.; Nardi, A.; Olney, J.W.; Sartorius, L.; Holtzman, D.M.

doi:10.1006/exnr.2001.7715

Cited by 157Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Behavioral phenotyping of GFAP-ApoE3 and -ApoE4 transgenic mice: ApoE4 mice show profound working memory impairments in the absence of Alzheimer’s-like neuropathology.

Hartman, R.E., Wozniak, D.F., Nardi, A., Olney, J.W., Sartorius, L., Holtzman, D.M.·2001·Experimental Neurology

DOI 10.1006/exnr.2001.7715

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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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ApoE4 mice were more severely impaired in working memory in a radial arm maze test.
“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
Compared with apoE3 transgenic mice, apoE4 transgenic mice were more severely impaired in learning and memory.
“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

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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.
ORCID: Hartman, R.E.
Wozniak, D.F.
Nardi, A.
Holtzman, D.M.
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2001-08
Volume: 170
Issue: 2
Pages: 326-344
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1006/exnr.2001.7715
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG11355-06, AG13956, P01AG011355)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › 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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Behavioral phenotyping of GFAP-ApoE3 and -ApoE4 transgenic mice: ApoE4 mice show profound working memory impairments in the absence of Alzheimer’s-like neuropathology.

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