BDNF expression mediates verbal learning and memory in women in a cohort enriched with risk for Alzheimer's disease

Abstract

Abstract INTRODUCTION This study examined whether sex differences in verbal learning and memory (VLM) are mediated by plasma brain‐derived neurotrophic factor (BDNF) expression. METHODS In a sample of n = 201 participants (63.81 ± 6.04 years, 66.2% female, 65.7% family history of Alzheimer's disease [AD], 38% apolipoprotein E [APOE] ε4+) from the Wisconsin Registry for Alzheimer's Prevention, VLM was measured using trials 3 through 5 and delayed recall from the Rey Auditory Verbal Learning Test. Plasma BDNF was measured using a Human BDNF Quantikine Immunoassay. Mediation analysis used bootstrapping, and stratified mediation models tested the conditional dependence of APOE ε4 carriage. RESULTS BDNF partially mediated the sex–VLM relationship (β = −0.07; 95% confidence interval [CI]: −0.18, −0.01). Female APOE ε4 carriers had higher VLM scores (β = −0.53; p = 0.03), while female non‐carriers had both higher BDNF levels (β = −0.68; p < 0.01) and VLM scores (β = −1.06; p < 0.01); BDNF was again a significant mediator (β = −0.18; 95% CI: −0.37, −0.05). DISCUSSION This study found that circulating BDNF mediates higher verbal memory scores in females—particularly in APOE ε4 non‐carriers. Highlights Sex differences in verbal learning and memory (VLM) were mediated by plasma brain‐derived neurotrophic factor (BDNF) levels. Women exhibited higher VLM scores and plasma BDNF levels compared to men. The protective effect of BDNF in women was attenuated by apolipoprotein E ε4 carriage. Findings suggest sex‐specific mechanisms against verbal memory decline in aging.

Keywords

• Alzheimer's disease
• apolipoprotein E ε4
• brain‐derived neurotrophic factor
• memory
• sex
• verbal learning