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Neurodegenerative disease

WNT receptor variant linked to synaptic degeneration

Nature Reviews Neurology volume 19, page 129 (2023)Cite this article

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A genetic variant of the WNT receptor LRP6 exacerbates synapse degeneration in mouse models of ageing and Alzheimer’s disease (AD), according to new research reported in Science Advances. The LRP6-Val variant, which results in replacement of isoleucine with valine at amino acid 1062 of LRP6, is associated with late-onset AD, and the findings provide clues to the mechanisms that could underlie this relationship.

“The LRP6-Val variant produces defects in WNT signalling in cell lines, but its impact on the brain and in AD has not been reported,” comments Patricia Salinas, who led the new study. “We decided to generate a knock-in mouse carrying this variant to examine its effects on neuronal connectivity in the context of ageing and AD.”

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References

Original article

  • Jones, M. E. et al. A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer’s disease. Sci. Adv. 9, eabo7421 (2023)

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Related articles

  • Tzioras, M. et al. Synaptic degeneration in Alzheimer disease. Nat. Rev. Neurol. 19, 19–38 (2023);

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  • De Ferrari, G. V. et al. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer’s disease. Proc. Natl Acad. Sci. USA 104, 9434–9439 (2007)

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Nature Reviews Neurology http://www.nature.com/nrneurol/

    Heather Wood

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  1. Heather Wood
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Correspondence to Heather Wood.

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Wood, H. WNT receptor variant linked to synaptic degeneration. Nat Rev Neurol 19, 129 (2023). https://doi.org/10.1038/s41582-023-00781-7

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