ABSTRACT Background: Emerging evidence suggests that metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) may increase vulnerability to neurodegenerative disorders. However, the link between PCOS and Alzheimer’s disease (AD)-related pathology remains unclear. Methods: In this cross-sectional study, plasma levels of β -amyloid (Aβ 40 , Aβ 42 ), phosphorylated tau (p-tau181), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified in women with PCOS and age-matched controls. Homeostasis model assessment of insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, TNF- α) and hormonal parameters were assessed. Mediation and moderation analyses were conducted to explore metabolic and hormonal pathways underlying biomarker alterations. Results: Among 400 women (200 PCOS, 200 controls), age and BMI were comparable ( P > 0.05). Compared with controls, PCOS participants had increased Aβ 40 , p-tau181, NfL and GFAP, a slightly higher Aβ 42 , and a lower A β 42 / 40 ratio ( all P < 0.05). p-tau181 correlated positively with HOMA-IR ( r = 0.41) and IL-6 ( r = 0.36), while Aβ 42 / 40 ratio correlated negatively with HOMA-IR ( r = –0.27). In multivariable analysis, p-tau181 (aOR = 1.34, 95% CI 1.05–1.71), IL-6 (aOR = 1.19) and TNF- α (aOR = 1.14) were independent predictors of insulin resistance. Mediation analysis indicated that HOMA-IR, IL-6 and TNF- α jointly mediated ∼ 71% of the PCOS–p-tau181 association, suggesting a metabolic–inflammatory pathway linking PCOS to AD-related tau pathology. Conclusions: PCOS is linked to peripheral markers of early Alzheimer’s pathology, largely mediated by insulin resistance and inflammation. PCOS may provide a clinical context to explore metabolic–inflammatory contributors to early neurodegenerative changes.
Xing et al. (Fri,) studied this question.