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

Topic/Product:
Alzheimer's, CNS Disease Panel 120, Dementia
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma

Abstract

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.

Authors and Affiliations

Joyce R. Chongᵃ˒ᵇ, Irwin K. Cheahᶜ˒ᵈ, Richard M. Tangᶜ˒ᵈ, Barry Halliwellᶜ˒ᵈ, Christopher P. Chenᵃ˒ᵇ, and Mitchell K.P. Laiᵃ˒ᵇ*

ᵃ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
ᵇ Memory Aging and Cognition Centre, National University Health System, Singapore 117577, Singapore
ᶜ Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
ᵈ Life Science Institute, Neurobiology Programme, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore

* Corresponding author

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.