Comparative Blood Profiling Based on ATR-FTIR Spectroscopy and Chemometrics for Differential Diagnosis of Patients with Amyotrophic Lateral Sclerosis—Pilot Study

Abstract

Amyotrophic lateral sclerosis (ALS) is a motor neurodegenerative disease characterized by poor prognosis. Currently, screening and diagnostic methods for ALS remain challenging, often leading to diagnosis at an advanced stage of the disease. This delay hinders the timely initiation of therapy, negatively impacting patient well-being. Additionally, misdiagnosis with other neurodegenerative disorders that present similar profiles often occurs. Therefore, there is an urgent need for a cost-effective, rapid, and user-friendly tool capable of predicting ALS onset. In this pilot study, we demonstrate that infrared spectroscopy, coupled with chemometric analysis, can effectively identify and predict disease profiles from blood samples drawn from ALS patients. The selected predictive spectral markers, which are used in various discriminant models, achieved an AUROC sensitivity of almost 80% for distinguishing ALS patients from controls. Furthermore, the differentiation of ALS at both the initial and advanced stages from other neurodegenerative disorders showed even higher AUROC values, with sensitivities of 87% (AUROC: 0.70–0.97). These findings highlight the elevated potential of ATR-FTIR spectroscopy for routine clinical screening and early diagnosis of ALS.

Keywords

• amyotrophic lateral sclerosis
• infrared spectroscopy
• metabolic signatures
• patient stratification
• chemometrics
• classification strategy