- December 4, 2025
- Nick Kanaan, et al., Michigan State University
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma
Abstract
INTRODUCTION Accurate antemortem differentiation among dementia etiologies remains challenging, particularly for atypical or mixed clinical presentations. Multiplexed plasma proteomics paired with supervised machine-learning offers a minimally invasive and accessible approach for differential diagnosis.
METHODS Plasma from 194 participants was analyzed using the NULISA CNS 120+ plasma biomarker panel. Differentially abundant protein patterns associated with AD, frontotemporal lobar degeneration, Lewy body disease, and vascular disease were identified. These features were used to train supervised XGBoost classifier models. Models were then applied to participants with mild cognitive impairment to generate data-driven predictions of etiology.
RESULTS NULISA plasma biomarkers revealed disease-specific protein patterns. XGBoost classifiers differentiated disease etiologies with high specificity. Application of the models to participants with mild cognitive impairment yielded robust etiologic predictions.
DISCUSSION These results support the feasibility of using multiplexed NULISA plasma proteomics, combined with machine learning, for differential diagnosis of complex neurodegenerative dementia etiologies.
Highlights
Multiplex plasma proteomics revealed distinct protein markers of dementia subtypes
Supervised XGBoost classifiers accurately distinguished each dementia etiology
Model application to unknown etiologies produced interpretable probability profiles
The combined NULISA-machine learning framework demonstrates diagnostic feasibility
Authors & Affiliations
Kelly N. DuBois¹², Subhamoy Pal², Amanda Cook Maher²³, Judith Heidebrink²⁴, Carol Persad³, Bruno M. Giordani²³, Benjamin M. Hampstead²⁵⁶, Kelly M. Bakulski², David G. Morgan¹²⁷, and Nicholas M. Kanaan¹²⁷*
¹ Department of Translational Science and Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA
² Michigan Alzheimer’s Disease Research Center, University of Michigan, Ann Arbor, MI, USA
³ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
⁴ Department of Neurology, University of Michigan, Ann Arbor, MI, USA
⁵ Research Program on Cognition and Neuromodulation Based Interventions (RP-CNBI), Departments of Psychiatry & Neurology, University of Michigan, Ann Arbor, MI, USA
⁶ VA Ann Arbor Healthcare System, Neuropsychology Section, Mental Health Service, Ann Arbor, MI, USA
⁷ Neuroscience Program, Michigan State University, East Lansing, MI, USA