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Basic Science and Pathogenesis.

Anna L Tyler1, Dylan Garceau1, Kevin P Kotredes1

  • 1The Jackson Laboratory, Bar Harbor, ME, USA.

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Summary
This summary is machine-generated.

The protective klotho (KL) VS variant in mice influences gene expression related to synaptic function and protein translation, offering insights into aging and Alzheimer's Disease (AD) mechanisms.

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Area of Science:

  • Neuroscience
  • Genetics
  • Aging Research

Background:

  • The klotho (KL) VS haplotype is linked to reduced Alzheimer's Disease (AD) risk and pathology.
  • Human KL variants (common FC and protective VS) were introduced into mice to study their AD-related effects.

Purpose of the Study:

  • To investigate the impact of human klotho (KL) variants on Alzheimer's Disease (AD) pathology.
  • To establish a translatable mouse model for studying KL's role in aging and AD.

Main Methods:

  • Generated homozygous and heterozygous mice for human KL variants (FC and VS) alongside wild-type (FS).
  • Measured whole brain gene expression at 4 and 12 months to identify differentially expressed genes.

Main Results:

  • No gene expression differences were observed at 4 months.
  • At 12 months, 609 differentially expressed genes were identified, enriched for synaptic function and protein translation.
  • The protective VS allele modulated synapse-related and ribosome/translation-related genes.

Conclusions:

  • KL human variants in mice provide a valuable model for understanding KL's role in aging and AD.
  • These findings highlight KL's influence on synaptic and translational pathways relevant to neurodegeneration.