Back to Publications​
Publication
Acta Neuropathologica

A plasma protein signature for cerebral amyloid angiopathy

Back to Publications​
  • May 20, 2026
  • Nicholas Ashton, et al., Banner Health
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma

Abstract

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β (Aβ) in the walls of leptomeningeal and cortical blood vessels that increases risk of intracerebral hemorrhages and progressive cognitive decline. More than 90% of individuals with Alzheimer’s disease (AD) exhibit some level of CAA. Notably, in the new era of disease-modifying treatments for AD, CAA is a significant risk factor for amyloid-related imaging abnormalities (ARIA), an adverse event associated with anti-amyloid treatments. Therefore, there is great need for accessible, reliable and accurate in vivo biomarkers (e.g., blood-based) to improve antemortem identification of CAA that would improve risk stratification and reduce symptomatic ARIA. In this study, we employed the Nucleic Acid-Linked Immuno-Sandwich Assay (NULISA™) central nervous system panel for exploratory biomarker quantification in antemortem plasma of participants with neuropathological assessments for CAA from the Banner Sun Health Research Institute Brain and Body Donation Program (N = 251) and independently validated in the University of California Irvine Alzheimer Disease Research Center cohort (N = 110). We evaluated the differential protein expression in antemortem plasma sample taken < 5 years (mean 1.76 ± 1.3) from death using a logistic regression model. We further compared multi-biomarker models and found that a combination of CRP, IL4, CCL11, NPY and PDLIM5, plus demographic covariates showed an area under the curve (AUC) of 0.90 (95% CI 0.86–0.94) to identify neuropathologically confirmed CAA in the discovery cohort. In our independent replication, the antemortem plasma signature performed better than the basic demographics model showing a potential to predict CAA. The exploration and validation in antemortem plasma indicate that a multi-analyte panel, when combined with in vivo blood biomarkers for AD pathology, may be capable of identifying the presence of CAA and could have an meaningful impact on the clinical evaluation of patients under the investigation for cognitive decline. Further developments in biomarkers for this condition are crucial so that CAA identification could inform treatment decisions by highlighting ARIA risk.

Read the Publication

Authors & Affiliations

Alpana Singh1 · Marisa N. Denkinger1 · Antoine Leuzy1 · Kari Dieckhoff1 · Jame Liu1 · Taina M. Marques1 · Edwin Monuki2,3 · Craig Stark3 · Joshua D. Grill3,4 · Christy Hom3,5 · David Sultzer3,5 · Eric Doran3,6 · Ira Lott3,7 · Kevin Wood3 · Brianna Gawronski3 · Lourdes Gonzalez3 · Parichita Choudhury1 · Alireza Atri1,9,10 · Thomas G. Beach1 · Geidy E. Serrano1 · S. Ahmad Sajjadi3,7 · Kendall Van Keuren‑Jensen8 · Eric M. Reiman9 · Elizabeth Head2,3 · Nicholas J. Ashton1,9,11

1 Fluid Biomarker Program, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA
2 Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA
3 Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA 
4 Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA
5 Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697, USA
6 Department of Pediatrics, University of California, Irvine, CA 92697, USA
7 Department of Neurology, University of California, Irvine, CA 92697, USA
8 Neurogenomics Division, TGEN, Phoenix, AZ 85004, USA
9 Banner Alzheimer’s Institute, Phoenix, AZ 85006, USA
10 Department of Neurology, Mass General Brigham and Harvard Medical, Boston 92114, USA
11 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden

Linkedin

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.

Linkedin

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.