Sex differences in CSF biomarkers vary by Alzheimer’s disease stage and APOE ε4 genotype

Objective: To evaluate sex-differences in cerebrospinal fluid (CSF) biomarkers, taking the potential modifying role of clinical disease stage and APOE-e4 genotype into account. Method: We included participants (n=1801) with probable AD dementia (n=937), Mild Cognitive Impairment (MCI; n=437) and Subjective Cognitive Decline (SCD; n=427). Main outcomes were CSF amyloid β1-42 (Aβ42), total tau (t-Tau) and tau phosphorylated at threonine 181 (p-Tau) levels. Age corrected three-way interactions between sex, disease stage (i.e. syndrome diagnosis at baseline) and APOE-e4 were tested with linear regression analyses for each outcome measure. In case of significant interactions (p Results: Three-way interactions were significant for total Tau (p Conclusions: Within APOE-e4 carriers, sex-differences in CSF (p)Tau are more evident in early disease stages, whereas for APOE-e4 non carriers sex-differences are more evident in advanced disease stages. These findings suggest that the effect of APOE-e4 on sex-differences in CSF biomarkers depends on disease stage in AD.