Upregulation of sFRP1 Is More Profound in Female than Male 5xFAD Mice and Positively Associated with Amyloid Pathology

J Alzheimers Dis. 2023;95(2):399-405. doi: 10.3233/JAD-230218.

Abstract

The prevalence of Alzheimer's disease is greater in women, but the underlying mechanisms remain to be elucidated. We herein demonstrated that α-secretase ADAM10 was downregulated and ADAM10 inhibitor sFRP1 was upregulated in 5xFAD mice. While there were no sex effects on ADAM10 protein and sFRP1 mRNA levels, female 5xFAD and age-matched non-transgenic mice exhibited higher levels of sFRP1 protein than corresponding male mice. Importantly, female 5xFAD mice accumulated more Aβ than males, and sFRP1 protein levels were positively associated with Aβ42 levels in 5xFAD mice. Our study suggests that sFRP1 is associated with amyloid pathology in a sex-dependent manner.

Keywords: 5xFAD mice; Alzheimer’s disease; AβPP; amyloid-β; sFRP1; sex-dependent effects.

Publication types

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

MeSH terms

  • ADAM10 Protein / genetics
  • ADAM10 Protein / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor* / genetics
  • Amyloid beta-Protein Precursor* / metabolism
  • Amyloidogenic Proteins / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Up-Regulation

Substances

  • ADAM10 Protein
  • Amyloid
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Amyloidogenic Proteins
  • Aspartic Acid Endopeptidases
  • Sfrp1 protein, mouse