Novel blood-based proteomic signatures across multiple neurodegenerative diseases

INTRODUCTION: Blood-based biomarkers have the potential to support early and accurate diagnosis of neurodegenerative diseases, which is sensitive to molecular pathology and predictive of outcome. We evaluated a novel multiplex proteomic method in people with diverse neurodegenerative diseases. METHODS: Serum from people with Alzheimer’s disease (N=36), Lewy body dementia (N=34), frontotemporal dementia (N=36) and progressive supranuclear palsy (N=36) and age-matched controls (N=30) was analysed with the NUcleic acid Linked Immuno- Sandwich Assay (NULISA) central nervous system panel (~120 analytes) and inflammation panel (250 analytes). Biomarkers were compared across groups and included as predictors of survival. RESULTS: The NULISA panels demonstrated high sensitivity and reliability for detecting multiple biomarkers across neurodegenerative disorders. There were condition-specific proteomic biomarkers, while NfL, CRH, CD276 and a data-driven inflammation pattern were significant transdiagnostic outcome predictors. DISCUSSION: The sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia-related biomarkers.