Marked regional differences of brain human apolipoprotein e expression in targeted replacement mice

Sullivan, P.M; Mace, B.E; Maeda, N; Schmechel, D.E

doi:10.1016/j.neuroscience.2003.10.011

Cited by 113Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function Studies

Marked regional differences of brain human apolipoprotein e expression in targeted replacement mice

Sullivan, P.M, Mace, B.E, Maeda, N, Schmechel, D.E·2004·Neuroscience

DOI 10.1016/j.neuroscience.2003.10.011

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Abstract

We used three human apolipoprotein (apo) E targeted replacement mouse lines, each expressing one of the three common human apoE isoforms to study the pattern of apoE expression in the central nervous system (CNS). Immunocytochemistry on brain sections from all three lines of targeted replacement mice, wild type mice, African green monkeys, and humans show a predominantly glial pattern of apoE expression. The levels of human apoE protein in hippocampus and frontal cortex were similar between targeted replacement mice and non-demented human tissue. Within a given brain region, the levels of apoE were very similar amongst all three isoforms, which contrasts sharply with plasma, where apoE2 levels are 16-fold higher than apoE3 and E4 levels. Across brain regions, cerebellar apoE levels were significantly higher than cerebral apoE levels. In conclusion, we provide detailed analysis of a human apoE animal model system that recapitulates both the pattern and level of apoE expression in non-demented humans. The neurobiology of human apoE isoforms can now be studied in both the normal and post-injury state, since all apoE regulatory sequences are intact. Finally, the differences in apoE levels we observed may explain the regional vulnerability of neuronal degeneration in Alzheimer's disease.

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APOE targeted replacement mice express human APOE in place of their mouse Apoe gene and do not develop overt AD pathology.
“APOE targeted replacement mice, which express human APOE in place of their mouse Apoe gene and which do not develop overt AD pathology28,29”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [28]
Human ApoE protein is predominantly expressed in glia in hApoE-TR mice, recapitulating the pattern of ApoE expression in non-demented human brains.
“Additionally, immunohistochemistry analyses revealed that human ApoE protein is predominantly expressed in the glia, which recapitulates the pattern of ApoE expression in the non-demented human brains (Sullivan et al., 2004).”
From Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention (2018) · cites this paper as Sullivan et al., 2004
An initial study characterizing human apoE knock-in mice suggested that apoE levels in the mouse brains were not significantly different among the apoE2, apoE3, and apoE4 isoforms.
“An initial study characterizing such mice suggested that apoE levels in the mouse brains were not significantly different among the apoE2, apoE3, and apoE4 isoforms (Sullivan et al., 2004).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Sullivan et al., 2004

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Authors: Sullivan, P. M., Mace, B. E., Maeda, N., & Schmechel, D. E.
Affiliations: Duke University (US)
University of North Carolina at Chapel Hill (US)
Corresponding author: Sullivan, P.M
ORCID: Sullivan, P.M
Mace, B.E
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2004-01
Volume: 124
Issue: 4
Pages: 725-733
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2003.10.011
OpenAlex: W1982180106
Cited by: 113
References: 11
Citations by year: 2026: 5 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 7
FWCI: 2.34
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: Syracuse University
National Institute on Aging (P50AG005128, P50 AG05128-18)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: apolipoprotein E, APOE isoforms, targeted replacement mice, regional brain differences, glial expression, hippocampus, frontal cortex, cerebellum, Alzheimer's disease, neuronal vulnerability
MeSH terms: Aged, Alleles, Animals, Apolipoproteins E, Brain, Chlorocebus aethiops, Humans, Immunohistochemistry, Male, Mice, Transgenic, Neuroglia, Tissue Distribution, Blotting, Western, Mice

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Marked regional differences of brain human apolipoprotein e expression in targeted replacement mice

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