The Relationship between Ergothioneine, Allantoin and Neocortical Amyloid Load

Alzheimer's disease (AD) is characterised by hallmark pathology of amyloid beta (Aβ) plaques and hyperphosphorylated tau neurofibrillary tangles in the brain. Ergothioneine (ET) is a potent antioxidant, and anti-inflammatory compound that has shown potential as a therapeutic for neurodegenerative disease*. Cross-sectional analyses of cognitively normal individuals aged 65-90yrs from the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort were stratified by amyloid status (Aβ+, SUVR >1.35). Plasma ET, its metabolites and urinary allantoin, were quantified by liquid chromatography-mass spectrometry. Plasma Aβ1-40, Aβ1-42, GFAP, and NFL were measured by SIMOA and pTau181 and pTau231 were measured via ELISA. No differences in plasma ET or metabolites were observed between AB- (n=65) and AB+ (n=35) groups. Partial correlation analysis highlighted positive correlations between allantoin, and NFL (r = 0.40, pFDR < 0.01), pTau181 (r = 0.47, pFDR < 0.01) and GFAP (r = 0.31, pFDR = 0.01). Partial correlation by subgroup, revealed positive correlations between plasma ET (r = 0.48, pFDR = 0.05) with Aβ42/40 in the AB+ group only. Evidence indicates that ET may protect the brain from oxidative damage and neuroinflammation. Higher urinary allantoin levels were associated with higher plasma AD biomarkers. Further, plasma ET levels were higher in individuals with a higher AB42/40 ratio, within the AB+ group, suggestive that high ET may potentially have neuroprotective effects. More research will be imperative to validate the significance of ET as a therapeutic for prevention of cognitive decline.