Molecular biomarkers for multiple system atrophy. (A systematic review)

Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder. Early diagnosis remains challenging because of clinical heterogeneity and symptom overlap with Parkinson’s disease and other atypical parkinsonian syndromes. This systematic review synthesizes current evidence on molecular biomarkers of MSA in biological fluids, including cerebrospinal fluid and blood plasma, following PRISMA 2020 guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). It evaluates seven groups of potential biomarkers: aggregated α-synuclein, neurofilament light chains, tau protein, myelin basic protein, neurotransmitters (dopamine, norepinephrine, serotonin, β-endorphins), neuroinflammation markers (cytokines, c), homocysteine, and coenzyme Q10. The review critically assesses their pathophysiological relevance, differential diagnostic and prognostic value, and the limitations and inconsistencies that hinder clinical implementation. It also discusses promising strategies for combining biomarkers.