Plasma Proteomic Classification of Alzheimer Disease, Parkinson Disease, and Amyotrophic Lateral Sclerosis Using a Single Neurodegeneration Panel: A Diagnostic Cohort Study
- 1Keio University School of Medicine, Keio Hospital
Abstract
ImportanceBlood 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.
ObjectiveTo 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 ParticipantsSingle-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).
ExposuresPlasma 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 MeasuresHold-out receiver operating characteristic area under the curve(AUC). Sensitivity and specificity at a training-set Youden threshold locked for Test.
ResultsHold-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 RelevanceA 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 PointsO_ST_ABSQuestionC_ST_ABSCan a single plasma neurodegeneration panel classify Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) in a heterogeneous neurological cohort?
FindingsIn 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.
MeaningA single plasma neurodegeneration panel can simultaneously support disease-selective classification of AD, PD, and ALS, offering a unified approach to blood-based diagnosis.
Related
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- Cerebrospinal fluid amyloid and neurodegeneration biomarkers in the diagnosis and prognosis of amyotrophic lateral sclerosis: a multicohort observational study
- Early Diagnostic Classification of Alzheimer's Disease Using Structural and Resting-State Functional MRI.
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- Plasma Proteomic Signatures Predict Incident Amyotrophic Lateral Sclerosis: A Prospective Study Stratified by C9orf72 Expansion.
BibTeX
@misc{okada2026plasma,
title = {{Plasma Proteomic Classification of Alzheimer Disease, Parkinson Disease, and Amyotrophic Lateral Sclerosis Using a Single Neurodegeneration Panel: A Diagnostic Cohort Study}},
author = {K. Okada and S. Shimohama and R. Okochi and S. Bun and K. Takahata and H. Tabuchi and Y. Iwabuchi and T. Tezuka and T. Nukariya and S. Okusa and Y. Nihei and S. Morimoto and S. Takahashi and K. Tai and Y. Sato and J. Kuromitsu and J. Nakahara and M. Seki and H. Okano and M. Mimura and D. Ito},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.26365782},
url = {https://www.medrxiv.org/content/10.64898/2026.10.19.26365782v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Plasma Proteomic Classification of Alzheimer Disease, Parkinson Disease, and Amyotrophic Lateral Sclerosis Using a Single Neurodegeneration Panel: A Diagnostic Cohort Study
AU - K. Okada
AU - S. Shimohama
AU - R. Okochi
AU - S. Bun
AU - K. Takahata
AU - H. Tabuchi
AU - Y. Iwabuchi
AU - T. Tezuka
AU - T. Nukariya
AU - S. Okusa
AU - Y. Nihei
AU - S. Morimoto
AU - S. Takahashi
AU - K. Tai
AU - Y. Sato
AU - J. Kuromitsu
AU - J. Nakahara
AU - M. Seki
AU - H. Okano
AU - M. Mimura
AU - D. Ito
PY - 2026
DA - 2026/10/19
PB - medRxiv
DO - 10.64898/2026.10.19.26365782
UR - https://www.medrxiv.org/content/10.64898/2026.10.19.26365782v1
AB - ImportanceBlood 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. ObjectiveTo 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 ParticipantsSingle-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). ExposuresPlasma 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 MeasuresHold-out receiver operating characteristic area under the curve(AUC). Sensitivity and specificity at a training-set Youden threshold locked for Test. ResultsHold-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 RelevanceA 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 PointsO_ST_ABSQuestionC_ST_ABSCan a single plasma neurodegeneration panel classify Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) in a heterogeneous neurological cohort? FindingsIn 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. MeaningA single plasma neurodegeneration panel can simultaneously support disease-selective classification of AD, PD, and ALS, offering a unified approach to blood-based diagnosis.
ER -