Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer’s disease
Open accessAbstract
Herein, we tested a recently proposed working model of apolipoprotein E (apoE)-mediated sulfatide metabolism/trafficking/homeostasis with two well-characterized amyloid precursor protein (APP) transgenic (Tg) animal models of Alzheimer's disease (AD) (i.e., APP(V717F) and APPsw) on a wild-type murine apoE background or after being bred onto an Apoe(-/-) background. As anticipated, lipidomics analysis demonstrated that the sulfatide levels in brain tissues were reduced beginning at approximately 6 months of age in APP(V717F) Tg, Apoe(+/+) mice and at 9 months of age in APPsw Tg, Apoe(+/+) mice relative to their respective non-APP Tg littermates. This reduction increased in both APP Tg mice as they aged. In contrast, sulfatide depletion did not occur in APP Tg, Apoe(-/-) animals relative to the Apoe(-/-) littermates. The lack of sulfatide depletion in APP Tg, Apoe(-/-) mice strongly supports the role of apoE in the deficient sulfatide content in APP Tg, Apoe(+/+) mice. Collectively, through different animal models of AD, this study provides evidence for an identified biochemical mechanism that may be responsible for the sulfatide depletion at the earliest stages of AD.
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Sulfatide depletion is observed in the early stages of Alzheimer's disease and in amyloid model mice in an age-dependent manner.
“ApoE was shown to regulate the metabolism of sulfatide whose depletion was observed in the early stages of AD and amyloid model mice in an age-dependent manner (41, 42).”
From <i>APOE3</i> -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [42]
ApoE regulates the metabolism of sulfatide.
“ApoE was shown to regulate the metabolism of sulfatide whose depletion was observed in the early stages of AD and amyloid model mice in an age-dependent manner (41, 42).”
From <i>APOE3</i> -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [42]
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Self-citation
- Authors
- Cheng, H., Zhou, Y., Holtzman, D. M., & Han, X.
- Affiliations
- Washington University in St. Louis (US)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Han, Xianlin
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 31
- Issue
- 7
- Pages
- 1188-1196
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2873070
- OpenAlex
- W2091782008
- Cited by
- 79
- References
- 5
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 12 · 2020: 7 · 2019: 2 · 2018: 9 · 2017: 7 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG031675, R01 AG23168, R01AG023168, R01AG013956, R01AG-31675, R37AG013956, AG13956)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- apolipoprotein E, sulfatide, Alzheimer's disease, amyloid precursor protein transgenic mice, sulfatide metabolism, lipidomics, ApoE-deficient mice
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Brain, Brain Chemistry, Disease Models, Animal, Homeostasis, Lipoproteins, Mice, Transgenic, Models, Biological, Myelin Sheath, Sphingomyelins, Sulfoglycosphingolipids, Down-Regulation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Knockout, Lipid Metabolism, Mice
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