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A deep joint-learning proteomics model for diagnosis of six conditions associated with dementia
This research introduces ProtAIDe-Dx, a deep joint-learning proteomics model that leverages plasma proteomics to provide simultaneous probabilistic diagnoses across six dementia-associated conditions. Tested on a massive dataset of 17,187 patients and controls, the model achieved balanced classification accuracy of 70-95% and AUC >78% across all conditions. ProtAIDe-Dx significantly improved biomarker-based differential diagnosis, revealing disease heterogeneity, co-pathologies, and identifying key protein networks and discriminative proteins. This work highlights the potential of plasma proteomics for improving patient-level diagnostic workup with a single blood draw, offering a scalable, minimally invasive, and economical tool for neurodegenerative disease diagnosis.
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Diagnostic Accuracy Highlight
95% Balanced Classification Accuracy for ALS Diagnosis| Model | ALS | PD | Control | AD | FTD | Stroke |
|---|---|---|---|---|---|---|
| ProtAIDe-Dx | 95% | 92% | 83% | 81% | 72% | 70% |
| XGBoost | High | High | Med | Med | Low | Low |
| TabPFN | High | High | Med | Med | Low | Low |
Case Study: Identifying Comorbid AD and Lewy Body Pathology
A 75-80 year old male with subjective cognitive complaints, but objectively intact cognition, was analyzed. ProtAIDe-Dx predicted underlying comorbid AD and Lewy body pathologies. This was subsequently confirmed by positive PET scans (cortical Aβ burden and temporal tau pathology) and positive CSF SAA, demonstrating the model's ability to uncover hidden co-pathologies in early stages of impairment, crucial for targeted intervention.
Key Findings:
- ProtAIDe-Dx identified comorbid AD and Lewy Body pathologies.
- Predictions were confirmed by advanced imaging (PET) and CSF biomarkers (SAA).
- Highlights the model's utility in complex diagnostic scenarios.
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