Study Documents Prevalence of α-Synuclein Pathology in Movement Disorders and Neurodegenerative Diseases

Study results presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders demonstrated the prevalence of α-synuclein (αSyn) pathology across various movement disorders and neurodegenerative diseases. Results revealed that αSyn pathology is not limited to well-known synucleinopathies such as Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), but is also a co-pathology in Alzheimer disease (AD), tauopathies (TP), and idiopathic normal pressure hydrocephalus (iNPH).

Study participants were recruited from the Paracelsus-Elena Klinik in Kassel, Germany between 2008 and 2022 (N=605). Researchers followed established diagnostic criteria and performed comprehensive evaluations (eg, clinical examinations, lumbar punctures, levodopa response tests, imaging studies) to establish a clinical diagnosis in 583 participants. The SYNTap test (Amprion, San Diego, CA), a cerebrospinal fluid (CSF)-based αSyn seed amplification assay (αSyn-SAA), was used to assess αSyn-SAA positivity.

• αSyn-SAA positivity rates were highest in those diagnosed with PD (96.8%), DLB (94.7%), and MSA (91.9%).
• Moderate αSyn-SAA positivity was observed in participants with tauopathies (31.3%), AD (38.1%), vascular PD/vascular dementia (25.5%), and iNPH (27.5%)
• All PD cases with concomitant iNPH were αSyn-SAA positive (100%).
• Lower rates of αSyn-SAA positivity were observed in participants with chorea (14.3%), dystonia (11.1%), and cerebellar ataxia (8.0%).
• Participants with unresolved diagnoses exhibited the following rates of αSyn-SAA positivity: unclear dementia with movement disorder (80.0%), unclear neurodegeneration (42.9%), and unclear hypokinetic movement disorder (30.0%).

Study authors noted that the high rate of aSyn-SAA positivity in cases that did not meet diagnostic criteria for a specific disease demonstrates that these diseases consist of a complex interplay of proteinopathies and affected neuronal pathways.