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Cited by 67Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and Treatments

Association between Alzheimer’s disease pathogenesis and early demyelination and oligodendrocyte dysfunction

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Sun, Xiao-Hong, Dong, Yu-Xia, Zhang, Hui-Yu, Li, Hui-Yuan, Liu, Pei-Hui, Sui, Yi·2018·Neural Regeneration Research
DOI 10.4103/1673-5374.232486PMC PMC5998637
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Abstract

The APPSwe/PSEN1dE9 (APP/PS1) transgenic mouse model is an Alzheimer's disease mouse model exhibiting symptoms of dementia, and is commonly used to explore pathological changes in the development of Alzheimer's disease. Previous clinical autopsy and imaging studies suggest that Alzheimer's disease patients have white matter and oligodendrocyte damage, but the underlying mechanisms of these have not been revealed. Therefore, the present study used APP/PS1 mice to assess cognitive change, myelin loss, and corresponding changes in oligodendrocytes, and to explore the underlying mechanisms. Morris water maze tests were performed to evaluate cognitive change in APP/PS1 mice and normal C57BL/6 mice aged 3 and 6 months. Luxol fast blue staining of the corpus callosum and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for myelin basic protein (MBP) mRNA were carried out to quantify myelin damage. Immunohistochemistry staining for NG2 and qRT-PCR for monocarboxylic acid transporter 1 (MCT1) mRNA were conducted to assess corresponding changes in oligodendrocytes. Our results demonstrate that compared with C57BL/6 mice, there was a downregulation of MBP mRNA in APP/PS1 mice aged 3 months. This became more obvious in APP/PS1 mice aged 6 months accompanied by other abnormalities such as prolonged escape latency in the Morris water maze test, shrinkage of the corpus callosum, upregulation of NG2-immunoreactive cells, and downregulation of MCT1 mRNA. These findings indicate that the involvement of early demyelination at 3 months and the oligodendrocyte dysfunction at 6 months in APP/PS1 mice are in association with Alzheimer's disease pathogenesis.

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Authors
Sun, X.-H., Dong, Y.-X., Zhang, H.-Y., Li, H.-Y., Liu, P.-H., & Sui, Y.
Affiliations
Fourth Affiliated Hospital of China Medical University (CN)
ORCID
Sui, Yi
Venue
Neural Regeneration Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2018
Volume
13
Issue
5
Pages
908
ISSN
1673-5374 (ISSN-L)
DOI
10.4103/1673-5374.232486
PMC
PMC5998637
OpenAlex
W2805598377
Cited by
67
References
6
Citations by year
2026: 4 · 2025: 14 · 2024: 3 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 4
FWCI
4.13
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Neural Regeneration Research (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, demyelination, oligodendrocyte dysfunction, APP/PS1 mice, myelin basic protein, white matter injury, cognitive impairment, corpus callosum, oligodendrocyte precursor cells, pathogenesis

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