LINGO‐1 antibody ameliorates myelin impairment and spatial memory deficits in the early stage of 5 XFAD mice
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AIMS: Multiple evidence has indicated that myelin injury is common in Alzheimer's disease (AD). However, whether myelin injury is an early event in AD and the relationship between it and cognitive function is still elusive. METHODS: Spatial memory of 5XFAD mice was determined by Morris water maze at 1 and 3 months old. Meanwhile, the deposition of Aβ, the expression of myelin basic protein (MBP), LINGO-1, NgR, and myelin ultrastructure in many memory-associated brain regions were detected in one-month-old and three-month-old mice (before and after LINGO-1 antibody administration) using immunostaining, Western blot (WB), and transmission electron microscopy (TEM), respectively. RESULTS: No abnormal Aβ deposition was found in one-month-old 5XFAD mice. However, spatial memory deficits were proved in accordance with an obvious demyelination in memory-associated brain regions in one-month-old mice and both deteriorated with age. Administration of LINGO-1 antibody could obviously restore the myelin impairments in CA1 and DG region and partially ameliorate spatial memory deficits. CONCLUSIONS: Our results demonstrated that myelin injury was an early event in 5XFAD mice even prior to emergence of deposition of Aβ. Intervention with the LINGO-1 antibody could attenuate impaired spatial memory deficits by remyelination, which suggested that myelin injury was involved in spatial memory deficits and remyelination may be a potential therapeutic strategy in early stage of AD or mild cognitive impairments.
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In 5XFAD pathology, spine loss (4-9 months) occurs subsequent to cognitive dysfunction (3-6 months) and Aβ plaque formation (two months).
“An interesting observation in the progression of 5XFAD pathology is that spine loss (4–9 months) [62] occurs subsequent to cognitive dysfunction (3–6 months) [35,63,64,65,66] and Aβ plaque formation (two months) [67].”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [66]
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- Howtocitethisarticle: Wu D, Tang X, Gu L-H, et al. LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in the early stage of 5XFAD mice. CNS Neurosci Ther. 2018;24:381-393. https://doi.org/10.1111/cns.12809
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Self-citation
- Authors
- Wu, D., Tang, X., Gu, L., Li, X., Qi, X., Bai, F., Chen, X., Wang, J., Ren, Q., & Zhang, Z.
- Affiliations
- Zhongda Hospital Southeast University (CN)
- Department of Neurology Affiliated ZhongDa Hospital Neuropsychiatric Institute School of Medicine Southeast University Nanjing China
- Department of Neurology and Geriatrics Fujian Institute of Geriatrics Fujian Medical University Union Hospital Fuzhou China
- Huazhong University of Science and Technology (CN)
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2018-02-09
- Volume
- 24
- Issue
- 5
- Pages
- 381-393
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6489849
- OpenAlex
- W2791162754
- Cited by
- 64
- References
- 40
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 12 · 2020: 8 · 2019: 3
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81420108012)
- 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
- myelin damage, demyelination, remyelination, Alzheimer's disease, 5xFAD mice, spatial memory impairment, myelin basic protein, Nogo receptor, amyloid-beta deposition, CA1, dentate gyrus, early Alzheimer's disease, mild cognitive impairment
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Disease Models, Animal, Humans, Male, Membrane Proteins, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Myelin Sheath, Nerve Tissue Proteins, Disease Progression, Neuroprotective Agents, Nootropic Agents, Spatial Memory
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