Performance of SOBA-AD blood test in discriminating Alzheimer’s disease patients from cognitively unimpaired controls in two independent cohorts

• Published in: Scientific reports Vol. 14; no. 1; pp. 7946 - 13
• Main Authors: Chen, Amy, Shea, Dylan, Daggett, Valerie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/45/611; 692/53; 692/53/2421; 692/699/375/365; 692/699/375/365/1283; Alzheimer's disease; Antibodies; Biomarkers; Blood; Blood tests; Cognitive ability; Dementia; Discrimination; Disease; Humanities and Social Sciences; Instrumentation; multidisciplinary; Neurodegenerative diseases; Oligomers; Peptides; Plasma; Protein structure; Reagents; Science; Science (multidisciplinary); Secondary structure; β-Amyloid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-57107-w

Amyloid-beta (Aβ) toxic oligomers are critical early players in the molecular pathology of Alzheimer’s disease (AD). We have developed a Soluble Oligomer Binding Assay (SOBA-AD) for detection of these Aβ oligomers that contain α-sheet secondary structure that discriminates plasma samples from patients on the AD continuum from non-AD controls. We tested 265 plasma samples from two independent cohorts to investigate the performance of SOBA-AD. Testing was performed at two different sites, with different personnel, reagents, and instrumentation. Across two cohorts, SOBA-AD discriminated AD patients from cognitively unimpaired (CU) subjects with 100% sensitivity, > 95% specificity, and > 98% area under the curve (AUC) (95% CI 0.95–1.00). A SOBA-AD positive readout, reflecting α-sheet toxic oligomer burden, was found in AD patients, and not in controls, providing separation of the two populations, aside from 5 SOBA-AD positive controls. Based on an earlier SOBA-AD study, the Aβ oligomers detected in these CU subjects may represent preclinical cases of AD. The results presented here support the value of SOBA-AD as a promising blood-based tool for the detection and confirmation of AD.