The Relationship between Ergothioneine, Allantoin and Neocortical Amyloid Load

Area of Science:

• Neuroscience
• Biochemistry
• Gerontology

Background:

• Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaques and tau tangles.
• Ergothioneine (ET) is a potent antioxidant and anti-inflammatory compound with therapeutic potential for neurodegenerative diseases.

Purpose of the Study:

• To investigate the relationship between ergothioneine (ET) levels, its metabolites, and Alzheimer's disease (AD) biomarkers in cognitively normal older adults.
• To explore the potential neuroprotective effects of ET in the context of amyloid pathology.

Main Methods:

• Cross-sectional analysis of the KARVIAH cohort (n=100) aged 65-90 years, stratified by amyloid status (Aβ+).
• Quantification of plasma ET, metabolites, and urinary allantoin using liquid chromatography-mass spectrometry.
• Measurement of plasma Aβ1-40, Aβ1-42, GFAP, NFL, pTau181, and pTau231 using SIMOA and ELISA.

Main Results:

• No significant differences in plasma ET or metabolites were found between amyloid-negative (Aβ-) and amyloid-positive (Aβ+) groups.
• Urinary allantoin positively correlated with plasma AD biomarkers: NFL, pTau181, and GFAP.
• Within the Aβ+ group, plasma ET positively correlated with the Aβ42/40 ratio, suggesting a potential neuroprotective role.

Conclusions:

• Higher urinary allantoin is associated with increased plasma AD biomarkers.
• Plasma ET levels may be linked to a higher Aβ42/40 ratio in individuals with amyloid pathology.
• Further research is crucial to validate ET's therapeutic potential for preventing cognitive decline and AD.