Proteomic markers linking anxiety phenotypes to Alzheimer’s disease risk: a multi-analyte proteomic analysis

Product:

CNS Disease Panel 120

Topic:

Neurology

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Abstract

Importance: Anxiety phenotypes – rumination, global anxiety, and worry (RAW) – are increasingly associated with Alzheimer’s disease and related dementias (ADRD) risk, yet how anxiety phenotypes relate to coordinated, multi-system biology in the at-risk older adults is unknown.
Objective: To map associations between anxiety phenotypes and plasma proteomic profile across five ADRDrelevant biological domains in older adults with high anxiety symptoms.
Design, Setting, and Participants: Cross-sectional analysis of 110 older adults (aged 53-75 years) without dementia from the observational longitudinal RAW Brain study in Pittsburgh, Pennsylvania.
Main Outcome(s) and Measure(s): Plasma was profiled with the NULISAseq CNS panel. Principal component (PC) analysis was conducted with Horn’s parallel analyses across five ADRD-relevant biological domains (amyloid/tau pathology, inflammation, neurodegeneration, synuclein/synaptic disorders, and vascular) yielded 14 PCs (37.4-64.9% within-domain variance). Associations with each phenotype were tested by linear regression adjusted for age and sex, with Benjamini-Hochberg false discovery rate correction (p-FDR<0.05).
Results: A neurodegeneration component (higher neuronal pentraxins and neurofilament light, with lower neurogranin) was associated with all three phenotypes (rumination, β=0.26; global anxiety, β=0.39; worry, β=0.36; all p-FDR<0.05). Inflammatory, VEGF receptor-ligand, and phospho-tau versus amyloid-processing components showed phenotype-specific associations, most often with worry severity.
Conclusion and Relevance: Distinct anxiety phenotypes map onto dissociable plasma proteomic profiling, converging on a shared neurodegeneration axis reflecting neuronal injury, while diverging across neuroimmune, vascular, and proteostatic domains. These results point toward the biological heterogeneity of anxiety phenotypes as risk factors for ADRD. Further research is needed to clarify these biological pathways and explore targeted prevention strategies.

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Authors and Affiliations

Ana Paula Costa¹, Helmet T. Karim¹ ², Marissa F. Farinas¹, Mary M. Geissinger¹, Xuemei Zeng¹, Dana L. Tudorascu¹ ³, Meryl A. Butters¹, Thomas K. Karikari¹, Carmen Andreescu¹
¹ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
² Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
³ Department of Biostatistics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

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.