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

Article type: Short Communication

Authors: Macyczko, Jesse R.^{; 1} | Wang, Na^{; 1} | Lu, Wenyan | Jeevaratnam, Suren | Shue, Francis | Martens, Yuka | Liu, Chia-Chen | Kanekiyo, Takahisa | Bu, Guojun | Li, Yonghe^{; *}

Affiliations: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA

Correspondence: [*] Correspondence to: Yonghe Li, Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. Tel.: +1 904 953 2483; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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

DOI: 10.3233/JAD-230218

Journal: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 399-405, 2023