Associations between serum estradiol and estrone and Alzheimer's disease biomarkers: An analysis in female participants from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS).

INTRODUCTION

Postmenopausal estrogen decline may contribute to Alzheimer's disease (AD), but evidence linking circulating estrogens to cerebrospinal fluid (CSF) AD biomarkers remains limited.

METHODS

We analyzed 854 female participants from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study with baseline serum estradiol and estrone measured by liquid chromatography-tandem mass spectrometry and repeated CSF amyloid-beta 42 (Aβ42), phosphorylated tau 181 (pTau181), and total tau (tTau). Models used regression for cross-sectional analyses and mixed-effects models restricted to the 187 participants with follow-up, adjusted for age, body mass index, waist circumference, and hormone replacement therapy (HRT) use. We also tested apolipoprotein E ε4 (APOEε4) and amyloid moderation and conducted sensitivity analyses excluding current HRT users.

RESULTS

Neither hormone was associated with Aβ42. Higher estradiol was associated with lower baseline tau, especially among APOEε4 carriers, but not with tau change. In exploratory longitudinal analyses, estrone showed a modest association with slower pTau181 increase.

DISCUSSION: Findings suggest more consistent cross-sectional associations of estradiol with tau than with Aβ42; longitudinal findings were limited by attrition and should be interpreted as exploratory.