Objective: To evaluate the clinical characteristics and potential biomarkers associated with atypical parkinsonian syndromes.

Background: Atypical Parkinson syndromes (APS) are a heterogeneous group of neurodegenerative disorders with rapid disease progression, early postural instability, autonomic dysfunction and cognitive impairment. It includes Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), and Corticobasal Syndrome (CBS). Early and accurate differentiation remains challenging due to overlapping clinical features. Biomarkers are increasingly being explored to improve diagnostic accuracy, disease mechanisms, and early detection of the disease

Method: Patients with Atypical Parkinson syndromes were recruited at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore. All patients were diagnosed and classified as PSP, and MSA according to the Movement Disorder Society (MDS) diagnostic criteria. A total of 50 plasma samples (PSP=30, MSA =20) and 14 CSF samples (PSP=10, MSA=4) were examined for evaluation of different biomarkers such as Aβ40, Aβ42, Tau, Tau181, Tau217 and Nfl using SIMOA analysis.

Results: In CSF, pTau217 was significantly higher in PSP (0.082 pg/ml) compared to MSA (0.026 pg/ml) (p=0.0401). Amyloid markers and other tau measures showed no significant differences between groups, although Aβ40 and Aβ42 levels were relatively higher in PSP. In plasma, PSP-RS patients showed significantly higher Aβ40 and Aβ42 levels than PSP-nonRS (p<0.05), suggesting subtype-related differences. In PSP, age of onset correlated positively with Aβ40 and NfL, while disease severity correlated strongly with pTau217 (PSPRS: r=0.6947, p=0.002; UPDRS-III: r=0.6873, p=0.0023). In MSA, disease duration correlated with Aβ40 and Aβ42, and motor severity was associated with NfL (UMSARS-I: r=0.6611, p=0.0028) and pTau217(UMSARS-II: r=0.5884, p=0.0441; UPDRS-III: r=0.7203, p=0.011). Across groups, UPDRS-III also correlated with Aβ40 (p=0.0192) and pTau217 (p=0.011).

Conclusion: Our finding showed that the elevated CSF pTau217 in PSP than MSA suggests its potential as a biomarker for disease differentiation. Additionally, the associations of amyloid markers, NfL, and pTau217 with age of onset, disease duration, and motor severity indicate their relevance in disease progression and subtype-specific differences in APS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/fluid-biomarker-signatures-in-atypical-parkinsonian-syndromes-insights-into-neurodegeneration-and-clinical-heterogeneity/