Free Radical Biology & Medicine · Jun 25, 2026

Metabolism of the antioxidant micronutrient ergothioneine as a plasma biomarker of cognitive resilience in older people with Alzheimer's disease amyloid pathology

By Chong JR, Cheah IK, Tang RM et al.

BACKGROUND: Associations between dietary micronutrients and cognitive resilience to Alzheimer's disease (AD) amyloid pathology is currently unknown. We investigated whether plasma levels of L-ergothioneine (ET), its metabolite L-hercynine (HC), and their ratio (HC:ET, as an index of ET metabolism) affect known associations between biomarkers of amyloid pathology (p-Tau181 or p-Tau217) and cognitive decline. METHODS: 259 initially dementia-free participants recruited from memory clinics and the community in Singapore had baseline measurements of plasma p-Tau, ET, HC, as well as annual neuropsychological assessments for up to 5 years to derive cognitive trajectories based on Clinical Dementia Rating-Sum of Boxes (CDR-SB) slopes. RESULTS: High HC:ET attenuated the positive correlations between plasma p-Tau and CDR-SB slopes. Compared with participants with low amyloid burden, participants with high amyloid burden had higher risk of cognitive decline when HC:ET was low (Hazard ratio [HR] = 2.33, p = 0.002), but not when HC:ET was high (HR = 1.47, p = 0.32). CONCLUSION: The identification of ET metabolism as a novel biomarker of cognitive resilience supports further investigations into mechanisms underlying its neuroprotectant properties. ET should be further assessed as a potential candidate for countering amyloid pathology-associated cognitive decline.

doi.org/10.1016/j.freeradbiomed.2026.06.043Open access, accepted manuscriptPubMed 42349803Biomarkers