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Microbial Composition, Disease Trajectory and Genetic Background in a Slow Onset Model of Frontotemporal Lobar

Nathalie Daude1, Ivana Machado1, Luis Arce1

  • 1Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 8M8, Canada.

Biomolecules
|May 28, 2025
PubMed

Insights

Environmental factors, like gut microbes, influence tau neuropathology in P301L transgenic mice. Transplanted mice showed differing tau accumulation and survival rates based on their genetic background, suggesting broader impacts of protein aggregation.

Area of Science:

  • Neuroscience
  • Genetics
  • Microbiology

Background:

  • Neurodegenerative diseases like Alzheimer's are complex, involving tau pathology.
  • Transgenic mouse models (TgTauP301L) exhibit slow-onset neurodegeneration with neuroinflammation.
  • Heterogeneity in tau deposition exists even within inbred mouse strains.

Purpose of the Study:

  • To investigate the role of gut microbial genotypes in tau neuropathology.
  • To determine if environmental influences, such as fecal microbial transplantation, affect tau accumulation and survival in TgTauP301L mice.
  • To explore potential parallels between tauopathy and amyloid precursor protein (APP) aggregation models regarding strain-specific viability.

Main Methods:

  • Utilized congenic (Cg) sublines of TgTauP301L mice (C57BL6/Tac and 129SvEv/Tac).
  • Administered antibiotic treatments and performed fecal microbial transplantation.
  • Analyzed neuroanatomical tau deposition patterns and calculated net intercurrent loss (survival rates).

Main Results:

  • Gut microbial genotypes diverged within Cg sublines.
  • Transplanted Cg 129SvEv/Tac TgTauP301L mice showed control-like tau deposition.
  • Transplanted Cg C57BL6/Tac TgTauP301L mice exhibited altered rostral-caudal tau accumulation (p = 0.0001).
  • Cg C57BL6/Tac TgTauP301L cohorts had significantly higher intercurrent loss (28%) compared to 129SvEv/Tac counterparts (9%) (p = 0.0027).

Conclusions:

  • Environmental factors, particularly gut microbiota, can influence tau neuropathology in TgTauP301L mice.
  • Strain-specific differences in survival rates in TgTauP301L mice may reflect generalized responses to protein aggregation.
  • These findings highlight the importance of considering environmental and genetic background interactions in neurodegenerative disease models.
Keywords:
frontotemporal dementiainbred strainmicrobiomeneurodegenerationneuroinflammationprotein misfoldingtauopathytransgenic mouse

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