Toward alpha-synuclein seed amplification assay in clinical practice.

Area of Science:

• Neurology
• Biochemistry
• Clinical Diagnostics

Background:

• Seed amplification assays (SAAs) show high diagnostic accuracy for alpha-synucleinopathies.
• Current SAAs require in-house production of alpha-synuclein (aSyn), limiting clinical laboratory accessibility.
• This study introduces a cerebrospinal fluid (CSF) aSyn-SAA protocol using only commercially available reagents.

Purpose of the Study:

• To develop an accessible cerebrospinal fluid (CSF) alpha-synuclein seed amplification assay (aSyn-SAA) for routine clinical use.
• To evaluate the diagnostic performance of a commercial-reagent-only aSyn-SAA in a real-life clinical cohort.

Main Methods:

• Assessed 126 CSF samples from patients with Lewy body diseases (LBD), Alzheimer's disease (AD), and non-alpha-synucleinopathy controls.
• Utilized a novel aSyn-SAA protocol requiring only commercial reagents.
• Determined aSyn-SAA activity in all CSF samples.

Main Results:

• The commercial-only CSF aSyn-SAA achieved 100% specificity in distinguishing LBD patients from controls.
• Sensitivity for detecting LBD was 72.3%.
• A small percentage (14.3%) of Alzheimer's disease patients tested positive for aSyn.

Conclusions:

• The commercial-only CSF aSyn-SAA protocol demonstrates high specificity in a clinical setting, advancing the use of aSyn biomarkers.
• This accessible protocol represents a significant step toward implementing aSyn-SAA in routine diagnostics.
• Further considerations for technical aspects and prion-like risk management are necessary for widespread adoption.