Apolipoprotein E Dose-Dependent Modulation of β-Amyloid Deposition in a Transgenic Mouse Model of Alzheimer's Disease
Abstract
Susceptibility to the development of Alzheimer's disease (AD) is increased for individuals harboring one or more apolipoprotein E4 (apoE4) alleles. Even though several isoform-specific effects of apoE have been identified, the relationship between biochemical function and risk factor assessment remains unknown. Our previous studies have demonstrated that there is an equilibrium between cerebral spinal fluid (CSF) and plasma beta-amyloid (Abeta) and that amyloid plaques can modify this equilibrium. Trafficking of soluble central nervous system (CNS) Abeta is a very dynamic system that almost certainly is modulated by Abeta-binding proteins. Altered trafficking of the Abeta peptide might have a dramatic consequence as to whether the peptide is metabolized or begins to deposit within the brain. To gain a better understanding of the molecular mechanisms by which apoE influences AD pathogenesis and/or Abeta trafficking, we developed PDAPP transgenic mice that express different levels of human apoE3. Analysis of the soluble CNS pools of Abeta in young mice showed an apoE3 dose-dependent decrease in Abeta levels (E3-/- > E3-/- > E3+/+). In addition to the dose-dependent effects on soluble Abeta, by 15 mo of age there were highly significant differences in the amount of deposited Abeta between the genotypes (E3-/- > E3-/- > E3+/+). These data indicate that apoE3 provides a dose-dependent protective effect against Abeta deposition. This study suggests that increasing human apoE levels…
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A preliminary study suggests that APP transgenic mice heterozygous for apoE3 have more deposited Aβ in the brain in comparison to mice with two copies of the apoE3 allele.
“A preliminary study suggests that APP transgenic mice heterozygous for apoE3 have more deposited Aβ in the brain in comparison to mice with two copies of the apoE3 allele (DeMattos, 2004).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as DeMattos, 2004
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Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
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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
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- Authors
- DeMattos, R. B.
- Affiliations
- Eli Lilly (United States) (US)
- Corresponding author
- DeMattos, Ronald B.
- ORCID
- DeMattos, Ronald B.
- Venue
- Journal of Molecular Neuroscience
- Published
- 2004
- Volume
- 23
- Issue
- 3
- Pages
- 255-262
- ISSN
- 0895-8696 (ISSN-L)
- OpenAlex
- W2024564106
- Cited by
- 55
- References
- 8
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2014: 1 · 2013: 4 · 2012: 1
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, APOE3, amyloid-beta deposition, Alzheimer's disease, dose-dependent effects, amyloid plaques, cerebrospinal fluid, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Brain, Disease Models, Animal, Humans, Mice, Transgenic, Amyloid beta-Peptides, Mice
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