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Cited by 105Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Staging of Alzheimer's Pathology in Triple Transgenic Mice: A Light and Electron Microscopic Analysis

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Oh, Kwang-Jin, Perez, Sylvia E., Lagalwar, Sarita, Vana, Laurel, Binder, Lester, Mufson, Elliott J.·2010·International Journal of Alzheimer's Disease
DOI 10.4061/2010/780102PMC PMC2925282
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Abstract

The age-related pathological cascade underlying intraneuronal tau formation in 3xTg-AD mice, which harbor the humanAPPSwe,PS1M126V, andTauP301Lgene mutations, remains unclear. At 3 weeks of age, AT180, Alz50, MC1, AT8, and PHF-1 intraneuronal immunoreactivity appeared in the amygdala and hippocampus and at later ages in the cortex of 3xTg-AD mice. AT8 and PHF-1 staining was fixation dependent in young mutant mice. 6E10 staining was seen at all ages. Fluorescent immunomicroscopy revealed CA1 neurons dual stained for 6E10 and Alz50 and single Alz50 immunoreactive neurons in the subiculum at 3 weeks and continuing to 20 months. Although electron microscopy confirmed intraneuronal cytoplasmic Alz50, AT8, and 6E10 reaction product in younger 3xTg-AD mice, straight filaments appeared at 23 months of age in female mice. The present data suggest that other age-related biochemical mechanisms in addition to early intraneuronal accumulation of 6E10 and tau underlie the formation of tau filaments in 3xTg-AD mice.

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  • The 3xTg-AD mouse develops both amyloid-β and neurofibrillary tangles in a temporal and spatial pattern similar to human AD pathology.

    “It develops both amyloid-β (Aβ) and neurofibrillary tangles in a temporal and spatial pattern similar to human AD pathology [3–6].”

    From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [5]

    The Introduction and Discussion describe age-related amyloid and tau pathology across brain regions, and the Discussion compares plaque and tangle-bearing neuron morphology with human AD. The paper does not establish that the overall temporal and spatial pattern of both pathologies matches human AD; it also notes differences in tau pathology. Page numbers were not available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In 3xTg-AD mice, both Aβ and tau exhibit age- and region-dependent formation, with Aβ plaques appearing prior to tangles, which are extensive in older transgenic mice.

    “Both Aβ and tau exhibit age- and region-dependent formation in these mice, with Aβ plaques appearing prior to tangles, which are extensive in older transgenic mice.”

    From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [5]

    The Discussion (page unavailable) reports that Aβ plaques increase with age and that tau pathology varies by age and brain region. Plaques were observed before filamentous tau aggregates, but the paper does not establish that tangles are extensive in older mice; its Discussion reports straight tau filaments in aged mice. It also distinguishes these late filaments from tau immunoreactivity present before plaque deposition. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Aβ plaque and tau pathology are evident in 15-month-old TG mice, and significantly increased with age.

    “In our morphological analysis (Fig. 2 and 3), as previously described [3–6, 28], Aβ plaque and tau pathology are evident in 15-month-old TG mice, and significantly increased with age (online supplementary Fig.1 and 2).”

    From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [5]

    The Results (3.1 and 3.3; page unavailable) describe age-related increases in immunoreactivity and tau markers, and the Discussion (section 4; page unavailable) says Aβ plaque numbers increased with age. But this study did not examine 15-month-old mice—it sampled 8–9 and 18–20 months instead—and these passages do not establish a statistically significant increase in both plaque and tau pathology. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The 3xTg-AD mouse provides a robust model of Alzheimer's disease with region-dependent patterns of progressive amyloid-β and tau pathology.

    “The widely studied triple transgenic (3xTg-AD) mouse provides a robust model of Alzheimer’s disease (AD) with region dependent patterns of progressive amyloid-β (Aß) and tau pathology.”

    From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [5]

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Authors
Oh, K.-J., Perez, S. E., Lagalwar, S., Vana, L., Binder, L., & Mufson, E. J.
Affiliations
  • Rush University Medical Center (US)
  • Northwestern University (US)
Corresponding author
Mufson, Elliott J.
ORCID
Venue
International Journal of Alzheimer's Disease
Publisher
Wiley
Published
2010
Volume
2010
Pages
1-24
ISSN
2090-0252 (ISSN-L)
DOI
10.4061/2010/780102
PMC
PMC2925282
OpenAlex
W2109352508
Cited by
105
References
70
Citations by year
2026: 2 · 2025: 1 · 2024: 19 · 2023: 6 · 2022: 11 · 2021: 5 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 5
FWCI
4.55
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Alzheimer s Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Rush University
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
Alzheimer's disease, triple transgenic mice, 3xTg-AD mice, tau pathology, tau filaments, AT8 antibody, 6E10 antibody, amygdala, hippocampus, subiculum, presenilin 1, age-related diseases

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