CSF alpha-Synuclein Seed Amplification Assay results in routine clinically collected samples.

Area of Science:

• Neurology
• Biochemistry
• Diagnostic Medicine

Background:

• Lewy body pathology is detectable via alpha-synuclein-Seed Amplification Assay (αSyn-SAA) in cerebrospinal fluid (CSF) with high accuracy in research cohorts.
• The performance of αSyn-SAA in CSF samples from routine clinical practice, outside of controlled cohort studies, is not well understood.

Purpose of the Study:

• To assess the agreement between αSyn-SAA results in CSF and clinical diagnoses in patients encountered in routine clinical practice.
• To evaluate the diagnostic utility of αSyn-SAA in a diverse patient population with various neurological and psychiatric conditions.

Main Methods:

• A cross-sectional study involving 356 participants undergoing lumbar puncture for diagnostic or therapeutic reasons.
• Cerebrospinal fluid samples were analyzed using αSyn-SAA.
• Data included binary αSyn-SAA results, neurological examination findings, and structured medical history.

Main Results:

• αSyn-SAA was positive in all tested samples from patients diagnosed with Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure.
• The assay also detected αSyn-SAA in subsets of patients with Alzheimer's disease and normal pressure hydrocephalus.
• Results demonstrated high concordance between αSyn-SAA findings and clinical diagnoses for PD and DLB.

Conclusions:

• αSyn-SAA in CSF exhibits high concordance with clinical diagnoses of PD and DLB, similar to findings in cohort studies.
• These results support the potential diagnostic value of αSyn-SAA for routine clinical application.
• The assay's ability to detect Lewy body co-pathology across various neurodegenerative diseases presents both opportunities and challenges for interpretation.