Work

Plasma Proteomic Classification of Alzheimer Disease, Parkinson Disease, and Amyotrophic Lateral Sclerosis Using a Single Neurodegeneration Panel: A Diagnostic Cohort Study

Year: 2026

Type: preprint

Abstract: Importance Blood biomarkers for Alzheimer disease(AD), Parkinson disease(PD), and amyotrophic lateral sclerosis(ALS) are typically developed as disease-specific single-analyte tests. Whether one shared plasma panel can support disease-selective classification remains unclear. Objective To test whether the Olink Target 48 Neurodegeneration plasma panel, analyzed with disease-specific Elastic Net models, can discriminate AD, PD, and ALS in a heterogeneous neurological cohort. Design, Setting, and Participants Single-center diagnostic cohort study at Keio University Hospital, Tokyo, Japan. After quality control and one consent withdrawal, 302 participants were analyzed(healthy controls n = 62; AD continuum n = 93; PD n = 39; ALS n = 27; other neurological disorders n = 81) and allocated by diagnosis-stratified sampling into a discovery training set(n = 211) and a locked hold-out test set(n = 91). Exposures Plasma normalized protein expression from 42 assays retained after protein quality control. Plasma DOPA decarboxylase was excluded a priori from all classifiers because blood levels primarily reflect dopaminergic treatment exposure. Main Outcomes and Measures Hold-out receiver operating characteristic area under the curve(AUC). Sensitivity and specificity at a training-set Youden threshold locked for Test. Results Hold-out AUCs were 0.974(95% CI, 0.942-0.995) for AD, 0.926(0.820-1.000) for PD, and 0.995(0.980-1.000) for ALS. At locked Youden cutoffs, sensitivity was 0.929 (95% CI, 0.765-0.991) and specificity was 0.921 (95% CI, 0.824-0.974) for AD, 0.833 (95% CI, 0.516-0.979) and 0.975 (95% CI, 0.912-0.997) for PD, and 1.000 (95% CI, 0.631-1.000) and 0.940 (95% CI, 0.865-0.980) for ALS. Conclusions and Relevance A single plasma neurodegeneration panel supported disease-selective classification of AD, PD, and ALS in internal validation. Multicenter external validation is needed before clinical application. Key Points Question Can a single plasma neurodegeneration panel classify Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) in a heterogeneous neurological cohort? Findings In this diagnostic cohort study, disease-specific Elastic Net models derived from a single plasma panel enabled the discrimination of AD, PD, and ALS from other neurological disorders and healthy controls. Meaning A single plasma neurodegeneration panel can simultaneously support disease-selective classification of AD, PD, and ALS, offering a unified approach to blood-based diagnosis.

Source: medRxiv

DOI: 10.64898/2026.10.19.26365782