Cited by 10,359Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy

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Selenica, Maj-Linda B., Brownlow, Milene, Jimenez, Jeffy P., Lee, Daniel C., Pena, Gabriela, Dickey, Chad A., Gordon, Marcia N., Morgan, Dave·2013·Neurodegenerative Diseases

Abstract

BACKGROUND: We aimed to investigate the influence of oligomeric forms of β-amyloid (Aβ) and the influence of the duration of exposure on the development of tau phosphorylation. METHODS: Aβ oligomers were injected intracranially either acutely into 5-month-old rTg4510 mice and tissue was collected 3 days later, or chronically into 3-month-old mice and tissue was collected 2 months later. Several forms of phosphorylated tau (p-tau), GSK3 (glycogen synthase kinase-3) and microglial and astrocyte activation were measured. RESULTS: Acute injections of Aβ oligomers had no effect on p-tau epitopes but did result in elevation of phosphorylated/activated GSK3 (pGSK3). Chronic infusion of Aβ oligomers into the right hippocampus resulted in 3- to 4-fold elevations in several p-tau isoforms with no changes in total tau levels. A significant elevation in pGSK3 accompanied these changes. Microglial staining with CD68 paralleled the increase in tau phosphorylation, however, CD45 staining was unaffected by Aβ. Control experiments revealed that the infusion of Aβ from the minipumps was largely complete by 10 days after implantation. Thus, the elevation in p-tau 2 months after implantation implies that the changes are quite persistent. CONCLUSION: Soluble Aβ(1-42) oligomers have long-lasting effects on tau phosphorylation in the rTg4510 model, possibly due to elevations in GSK3. These data suggest that even brief elevations in Aβ production, may have enduring impact on the risk for tauopathy.

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  • The relationship between DTI-detected WM changes and histologically detected axonal loss has been observed in several animal and human studies.

    “The relationship between DTI-detected WM changes and histologically detected axonal loss has been observed in several animal and human studies 25, 51–54”

    From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [52]

    The Methods section describes immunohistochemistry, and the Results section describes the distribution of injected amyloid oligomers in mouse brain (pages unavailable). Neither addresses DTI-detected white-matter changes or their relationship to histologically detected axonal loss. Searches for DTI, white matter, and axonal loss found no passage supporting the attributed claim. (LLM, conf=0.75)

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  • Reductions in FA and increases in RAD correlate with axon loss in abnormal WM in both MCI and AD patients.

    “Similar to our findings, reductions in FA and increases in RAD were found to correlate with axon loss in abnormal WM in both MCI and AD patients 25,51–54”

    From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [52]

    The Introduction discusses amyloid–tau interactions in mouse models, not diffusion measures or white-matter injury in patients. Searches for FA, radial diffusivity, axon loss, MCI, and abnormal white matter found no passage in our copy addressing the claimed correlation. (LLM, conf=0.76)

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Authors
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D.
Affiliations
University of South Florida (US)
Venue
Neurodegenerative Diseases
Publisher
S. Karger AG
Published
2012-07-10
Volume
11
Issue
4
Pages
165-181
ISSN
  • 1660-2854 (ISSN-L)
  • 1660-2862
OpenAlex
W2082429191
Cited by
10,359
References
186
Citations by year
2026: 7 · 2025: 280 · 2024: 673 · 2023: 878 · 2022: 924 · 2021: 753 · 2020: 704 · 2019: 697 · 2018: 812 · 2017: 836 · 2016: 793 · 2015: 823 · 2014: 330 · 2013: 215 · 2012: 191
FWCI
334.15
Type
journal article
Language
en
Open access
Locations
  • Neurodegenerative Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (AG 15490, R01AG015490, R29AG010282)
  • National Institute of Neurological Disorders and Stroke (R01NS030352, NS76308, R01NS076308, R01NS073899)
  • National Center for Research Resources (S10RR025633)
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
amyloid-beta oligomers, tau phosphorylation, tauopathy, glycogen synthase kinase-3, rTg4510 mice, microglial activation, astrocyte activation, hippocampus, Alzheimer's disease
MeSH terms
CD68 Molecule, Animals, Disease Models, Animal, Hippocampus, Mice, Transgenic, Neurons, Peptide Fragments, Phosphorylation, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Amyloid beta-Peptides, tau Proteins, Leukocyte Common Antigens, Microglia, Tauopathies, Glycogen Synthase Kinase 3, Mice

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