LRP10 variants in progressive supranuclear palsy

Neurobiol Aging. 2020 Oct;94:311.e5-311.e10. doi: 10.1016/j.neurobiolaging.2020.04.016. Epub 2020 Apr 30.


The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort. Two patients from the discovery cohort and 8 patients from the validation cohort carried a rare, heterozygous, and possibly pathogenic LRP10 variant (p.Gly326Asp, p.Asp389Asn, and p.Arg158His, p.Cys220Tyr, p.Thr278Ala, p.Gly306Asp, p.Glu486Asp, p.Arg554∗, p.Arg661Cys). In conclusion, possibly pathogenic LRP10 variants occur in a small fraction of patients with PSP and may be overrepresented in these patients compared with controls. This suggests that possibly pathogenic LRP10 variants may play a role in the development of PSP.

Keywords: Genetics; LRP10; Progressive supranuclear palsy; Rare variants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Exome Sequencing
  • Exons
  • Female
  • Genetic Variation / genetics*
  • Humans
  • LDL-Receptor Related Proteins / genetics*
  • Male
  • Middle Aged
  • Supranuclear Palsy, Progressive / genetics*


  • LDL-Receptor Related Proteins
  • LRP10 protein, human