Cited by 96Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Exogenous induction of cerebral β-amyloidosis in βAPP-transgenic mice

Walker, Lary C, Callahan, Michael J, Bian, Feng, Durham, Robert A, Roher, Alex E, Lipinski, William J·2002·Peptides

Abstract

A key commonality of most age-related neurodegenerative diseases is the accumulation of aggregation-prone proteins in the brain. Except for the prionoses, the initiation and propagation of these proteopathies in vivo remains poorly understood. In a previous study, we found that the deposition of the amyloidogenic peptide Abeta can be induced by injection of dilute extracts of Alzheimeric neocortex into the brains of Tg2576 transgenic mice overexpressing the human beta-amyloid precursor protein. The present study was undertaken to assess the pathology after long-term (12 months) incubation, and to clarify the distinctive anatomical distribution of seeded Abeta-immunoreactivity. All mice were injected at 3 months of age; 5 months later, as expected, Abeta deposits were concentrated mostly in the injected hemisphere. After 12 months, abundant, transgene-derived Abeta deposits were present bilaterally in the forebrain, but plaque load was still clearly greater in the extract-injected hemisphere. There was also evidence of tau hyperphosphorylation in axons of the corpus callosum that had been injured by the injection, most prominently in transgenic mice, but also, to a lesser degree, in non-transgenic mice. Five months following injection of AD-extract, an isolated cluster of Abeta-immunoreactive microglia was sometimes evident in the ipsilateral entorhinal cortex; the strong innervation of the hippocampus by entorhinal cortical neurons suggests the possible spread of seeded pathology from the injection site via neuronal transport mechanisms. Finally, using India Ink to map the local dispersion of injectate, we found that Abeta induction is especially potent in places where the injectate is sequestered. The AD-seeding model can illuminate the emergence and spread of cerebral beta-amyloidosis and tau hyperphosphorylation, and thus could enhance our understanding of AD and its pathogenic commonalties with other cerebral proteopathies.

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Crossref · 10.1016/s0196-9781(02)00059-1

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Authors
Walker, L. C., Callahan, M. J., Bian, F., Durham, R. A., Roher, A. E., & Lipinski, W. J.
Affiliations
  • Pfizer (United States) (US)
  • Banner Sun Health Research Institute (US)
Corresponding author
Walker, Lary C
Venue
Peptides
Publisher
Elsevier BV
Published
2002-07
Volume
23
Issue
7
Pages
1241-1247
ISSN
0196-9781 (ISSN-L)
OpenAlex
W2055346376
Cited by
96
References
34
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 12 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 14 · 2012: 5
FWCI
0.80
Type
journal article
Language
en
Open access
closed
Locations
  • Peptides (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, Tg2576 mice, amyloid precursor protein, tau hyperphosphorylation, corpus callosum, entorhinal cortex, microglia, proteinopathies, axonal transport
MeSH terms
Amyloidosis, Animals, Axons, Cerebral Cortex, Corpus Callosum, Humans, Injections, Intraventricular, Mice, Transgenic, Time Factors, Amyloid beta-Protein Precursor, Microglia, Entorhinal Cortex, Mice

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