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Cited by 16Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

Amyloid plaque pathogenesis in 5XFAD mouse spinal cord: retrograde transneuronal modulation after peripheral nerve injury

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Li, Jian-Ming, Xue, Zhi-Qin, Deng, Si-Hao, Luo, Xue-Gang, Patrylo, Peter R., Rose, Gregory W., Cai, Huaibin, Cai, Yan +1 more·2013·Neurotoxicity Research
DOI 10.1007/s12640-012-9355-2PMC PMC3563929
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Abstract

The spinal cord is composed of distinct neuronal groups with well-defined anatomic connections. In some transgenic (Tg) models of Alzheimer's disease (AD), amyloid plaques develop in this structure, although the underlying cellular mechanism remains elusive. We attempted to explore the origin, evolution, and modulation of spinal β-amyloid (Aβ) deposition using Tg mice harboring five familiar AD-related mutations (5XFAD) as an experiential model. Dystrophic neuritic elements with enhanced β-secretase-1 (BACE1) immunoreactivity (IR) appeared as early as 2 months of age, and increased with age up to 12 months examined in this study, mostly over the ventral horn (VH). Extracellular Aβ IR emerged and developed during this same period, site-specifically co-existing with BACE1-labeled neurites often in the vicinity of large VH neurons that expressed the mutant human APP. The BACE1-labeled neurites almost invariably colocalized with β-amyloid precursor protein (APP) and synaptophysin, and frequently with the vesicular glutamate transporter-1 (VGLUT). Reduced IR for the neuronal-specific nuclear antigen (NeuN) occurred in the VH by 12 months of age. In 8-month-old animals surviving 6 months after a unilateral sciatic nerve transection, there were significant increases of Aβ, BACE1, and VGLUT IR in the VN of the ipsilateral relative to contralateral lumbar spinal segments. These results suggest that extracellular Aβ deposition in 5XFAD mouse spinal cord relates to a progressive and amyloidogenic synaptic pathology largely involving presynaptic axon terminals from projection neurons in the brain. Spinal neuritic plaque formation is enhanced after peripheral axotomy, suggesting a retrograde transneuronal modulation on pathogenesis.

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  • The reduced number of dystrophic neurites indicates decreased β-amyloid-driven axonal damage.

    “indicative of decreased β-amyloid-driven axonal damage [44–47]”

    From The protective PLCγ2-P522R variant mitigates Alzheimer’s disease-associated pathologies by enhancing beneficial microglial functions (2025) · cites this paper as [46]

    The Discussion (‘Spinal Aβ deposition largely correlates with glutamatergic axonopathy’; page not provided) identifies dystrophic neurites as axon terminals and reports that their abundance increases alongside Aβ deposits. This supports treating fewer dystrophic neurites as a sign of less axonal pathology, but the paper describes an association, not proof that β-amyloid drives the damage. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Li, J.-M., Xue, Z.-Q., Deng, S.-H., Luo, X.-G., Patrylo, P. R., Rose, G. W., Cai, H., Cai, Y., & Yan, X.-X.
Affiliations
  • Central South University (CN)
  • Southern Illinois University Carbondale (US)
  • National Institutes of Health (US)
Corresponding author
Yan, Xiao-Xin
ORCID
Venue
Neurotoxicity Research
Publisher
Springer Science and Business Media LLC
Published
2012-10-05
Volume
24
Issue
1
Pages
1-14
ISSN
  • 1029-8428 (ISSN-L)
  • 1476-3524
DOI
10.1007/s12640-012-9355-2
PMC
PMC3563929
OpenAlex
W2142924675
Cited by
16
References
5
Citations by year
2025: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2017: 2 · 2016: 2 · 2014: 3
FWCI
0.64
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neurotoxicity Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation
  • Illinois Department of Public Health
  • National Natural Science Foundation of China
  • National Institutes of Health
  • National Institute on Aging (ZIAAG000959, ZIAAG000944)
  • National Institute of Neurological Disorders and Stroke (R21NS056371)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
amyloid plaques, spinal cord, 5xFAD mice, Alzheimer's disease, amyloid-beta deposition, BACE1, peripheral nerve injury, sciatic nerve transection, axotomy, ventral horn, vesicular glutamate transporter, synaptophysin, APP, neuronal loss, neuropathology
MeSH terms
Age Factors, Animals, DNA-Binding Proteins, Male, Mice, Transgenic, Nerve Tissue Proteins, Nuclear Proteins, Retrograde Degeneration, Sciatic Nerve, Spinal Cord, Amyloid beta-Protein Precursor, Synaptophysin, Presynaptic Terminals, Vesicular Glutamate Transport Protein 1, Mice, Amyloid Precursor Protein Secretases, Plaque, Amyloid, Peripheral Nerve Injuries

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