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Basic Science and Pathogenesis.

Gareth R Howell1,2,3, Dylan Garceau2, Kevin P Kotredes2

  • 1University of Maine, Orono, ME, USA.

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Summary
This summary is machine-generated.

New mouse models, LOAD3 (APOE4) and LOAD3*E3 (APOE3), incorporate humanized amyloid-beta and tau genes for advanced Alzheimer's disease (AD) research. These models will accelerate the study of genetic and environmental risk factors in AD.

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Area of Science:

  • Genetics and genomics
  • Neuroscience
  • Animal models

Background:

  • Alzheimer's disease (AD) research relies on accurate animal models.
  • The MODEL-AD Consortium develops novel mouse models incorporating human AD risk factors.
  • Previous work established APOE allelic series and LOAD1/LOAD2 strains.

Purpose of the Study:

  • Introduce the LOAD3 (APOE4) and LOAD3*E3 (APOE3) mouse strains.
  • These strains are designed for enhanced preclinical studies of late-onset AD.
  • Facilitate evaluation of genetic and environmental risk factors for AD.

Main Methods:

  • Developed LOAD3 strains by combining APOE4/APOE3, humanized Aβ (hAβ), and humanized MAPT (hMAPT) alleles.
  • Utilized exon replacement and gene editing for allele creation.
  • Confirmed genotypes via PCR and sequencing; maintained as closed colonies.

Main Results:

  • LOAD3 and LOAD3*E3 strains are viable and fertile.
  • Ongoing phenotyping at multiple ages (4, 12, 18, 24 months) includes biomarker, multi-omics, and neuropathology assessments.
  • Initial data at 4 and 12 months will be presented.

Conclusions:

  • LOAD3 and LOAD3*E3 serve as advanced platform strains for AD preclinical research.
  • These models will aid in evaluating additional genetic and environmental risk factors for Alzheimer's disease and related dementias (ADRD).