Blood-based Biomarkers of Alzheimer’s Disease and Neurodegeneration in an Indigenous African Cohort using both SIMOA and NULISA Platforms

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

Abstract

Background

In low- and middle-income countries, Alzheimer’s disease and related dementias (ADRD) constitute a growing public health burden. Indeed, the lack of awareness and easy screening tools, such as blood-based biomarkers, leaves many patients undiagnosed. In this study, we explored the core biomarkers of AD in an indigenous African cohort (VALIANT) to assess their relevance and potential utility to aid clinical diagnosis.

Methods

Nigerian African older adults (n = 967; 50 years) participating in the VALIANT study completed a baseline cross-sectional evaluation with associated clinical diagnosis. We quantified phosphorylated tau (p-tau 217), glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and amyloid beta (Aβ42 and Aβ40) levels in plasma with both the Single Molecule Assay (SIMOA, Quanterix) and Nucleic acid-Linked Immuno-Sandwich Assay (NULISA, Alamar) platforms.

Results

In agreement with previous findings, core AD biomarkers were associated with disease severity both in clinical diagnostic and clinico-pathological groups, with stepwise increases of p-tau 217, NfL and GFAP from cognitively unimpaired (CU) to dementia (p < 0.05). These results were consistent across both SIMOA and NULISA platforms. Comparison between sexes showed higher levels of biomarkers in male participants across diagnostic groups. We identified a significant effect of apoE E4 proteotype on p-tau217 levels after adjusting for age and sex but no significant effect on the other AD biomarkers.

Conclusion

This first application of cutting-edge plasma AD biomarker immunoassay using two ultrasensitive platforms in an indigenous African cohort showed good concordance and underscores the relevance and utility of blood-based biomarkers of AD in diverse populations. Additionally, sex differences could unveil biological distinctions inherent in the African population.

Authors & Affiliations

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.