Associations among cognitive performance, VCAM-1, and GFAP in black adults: The ARCHES study

Topic/Product:
Alzheimer's
Disease Area:
Alzheimer's Disease, Cognitive Decline
Sample Type:
Plasma

Abstract

Astrocytic injury and endothelial activation are interconnected processes within the neurovascular system that may contribute to variability in cognitive performance among cognitively unimpaired adults. Glial fibrillary acidic protein (GFAP) reflects astrocytic injury, while vascular cell adhesion molecule-1 (VCAM-1) reflects systemic endothelial activation. We examined whether VCAM-1 modifies associations between GFAP and cognition in cognitively unimpaired Black adults. This cross-sectional analysis included 313 Black adults aged ≥ 45 years enrolled in the Aging Research Characterizing Health Exposome via Social Drivers (ARCHES) study. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC) as the primary outcome and the Montreal Cognitive Assessment (MoCA) as a secondary outcome. Plasma GFAP and VCAM-1 were quantified using ultrasensitive immunoassays (NULISA™; Alamar Biosciences). Gaussian generalized linear models tested main effects and a VCAM-1 × GFAP interaction, adjusting for age, sex, and years of education; sensitivity analyses additionally adjusted for the Area Deprivation Index (ADI), body mass index (BMI), and apolipoprotein E (APOE) ε4 genotype. VCAM-1 and GFAP did not show independent associations with PACC; however, the VCAM-1 × GFAP interaction was significant (β = −1.36 × 10⁻⁶, 95% CI: −2.43 × 10⁻⁶ to −2.94 × 10⁻⁷, p = 0.013; FDR p = 0.030; standardized β = −0.118) and remained significant after additional adjustment for ADI, BMI, and APOE ε4 status. Associations were not significant for MoCA. These findings suggest that VCAM-1 may modify the relationship between GFAP and cognitive performance in cognitively unimpaired Black adults.

Authors and Affiliations

Ramkrishna K. Singh Jean-Francois Trani a,* b,c,e a , Semere Bekena a , Alexis I.B. Walker , Ganesh M. Babulal a,d,e

a Department of Neurology, Washington University School of Medicine, St Louis, MO, USA 

b School of Public Health, Washington University in St Louis, MO, USA

c Interdisciplinary Laboratory of Economic Sociology, National Conservatory of Arts and Crafts, Paris, France

d Department of Neurology, Mayo Clinic, Rochester, MN, USA

e Department of Psychology, University of Johannesburg, Johannesburg, South Africa

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.