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Cited by 8Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Axonal Terminals Exposed to Amyloid-β May Not Lead to Pre-Synaptic Axonal Damage

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Sun, Shu-Wei, Nishioka, Christopher, Labib, Wessam, Liang, Hsiao-Fang·2015·Journal of Alzheimer’s Disease
DOI 10.3233/jad-142154PMC PMC4500050
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Abstract

Background: Synaptic deficits and neuronal loss are the major pathological manifestations of Alzheimer’s disease. However, the link between the early synaptic loss and subsequent neurodegeneration is not entirely clear. Cell culture studies have shown that amyloid-β (Aβ) applied to axonal terminals can cause retrograde degeneration leading to the neuronal loss, but this process has not been demonstrated in live animals. Objective: To test if Aβ applied to retinal ganglion cell axonal terminals can induce axonal damage in the optic nerve and optic tract in mice. Methods: Aβ was injected into the terminal field of the optic tract, in the left lateral geniculate nucleus of wildtype C57BL/6 mice. Following the injection, monthly diffusion tensor imaging was performed. Three months after the injection, mice underwent visual evoked potential recordings, and then sacrificed for immunohistochemical examination. Results: There were no significant changes seen with diffusion tensor imaging in the optic nerve and optic tract 3 months after the Aβ injection. The myelin and axons in these regions remained intact according to immunohistochemistry. The only significant changes observed in this study were delayed transduction and reduced amplitude of visual evoked potentials, although both Aβ and its reversed form caused similar changes. Conclusion: Despite the published in vitro studies, there was no significant axonal damage in the optic nerve and optic tract after injecting Aβ onto retinal ganglion cell axonal terminals of wildtype C57BL/6 mice.

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  • Evidence from AD tissue suggests early axonal dysfunction precedes overt cell loss, including dystrophic axons, dysfunctional axonal transport and cytoskeletal abnormalities early in the disease process.

    “This idea is bolstered by evidence from AD tissue, suggestive of early axonal dysfunction preceding overt cell loss. This includes the presence of dystrophic axons, dsyfunctional axonal transport and cytoskeletal abnormalities early in the disease process 62,63.”

    From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [62]

    The Introduction (page unavailable) describes early synaptic deficits before later neuronal loss and discusses axonal degeneration as a possible mechanism. It does not report dystrophic axons, dysfunctional axonal transport, or cytoskeletal abnormalities in AD tissue. Its own experiment was in mice, not AD tissue, and found no significant axonal damage after the tested exposure. (LLM, conf=0.86)

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Authors
Sun, S.-W., Nishioka, C., Labib, W., & Liang, H.-F.
Affiliations
  • University of California, Riverside (US)
  • Loma Linda University Medical Center (US)
  • Loma Linda University (US)
Corresponding author
Sun, Shu-Wei
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2015-04-13
Volume
45
Issue
4
Pages
1139-1148
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-142154
PMC
PMC4500050
OpenAlex
W1531226112
Cited by
8
References
3
Citations by year
2023: 2 · 2022: 1 · 2020: 2 · 2019: 1 · 2016: 2
FWCI
0.49
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS062830)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta, axonal injury
MeSH terms
Animals, Axons, Evoked Potentials, Visual, Female, Geniculate Bodies, Humans, Immunohistochemistry, Mice, Inbred C57BL, Microelectrodes, Myelin Sheath, Optic Nerve, Peptide Fragments, Retrograde Degeneration, Visual Cortex, Visual Perception, Amyloid beta-Peptides, Diffusion Tensor Imaging, Optic Tract

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