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CSF α-Synuclein Seed Amplification Assay in Patients With Atypical Parkinsonian Disorders
Chloe Anastassiadis1, Ivan Martinez-Valbuena1, Anna Vasilevskaya1
1From the Tanz Centre for Research in Neurodegenerative Diseases (C.A., I.M.-V., A.V., S.T., M.H., F.T., C. Sato, D.M., C.J.A., K.M., A.E.L., E.R., G.G.K., M.C.T.); Krembil Brain Institute (I.M.-V., A.M.-R., B.C., D.F.T.-W., A.E.L., S.H.F., G.G.K., M.C.T.); The Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (I.M.-V., A.M.-R., B.C., A.E.L., S.H.F., G.G.K., M.C.T.); Rossy Progressive Supranuclear Palsy Centre (I.M.-V., A.M.-R., A.E.L., G.G.K., M.C.T.), University Health Network and the University of Toronto; and University Health Network Memory Clinic (D.M.-F., C. Salvo, D.F.T.-W.), Toronto, Ontario, Canada.
Alpha-synuclein seed amplification assays (αSyn-SAA) detected αSyn copathology in corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) patients. This assay shows promise for identifying neuropathologic processes in these neurodegenerative diseases.
Area of Science:
- Neuroscience
- Neuropathology
- Biomarker Discovery
Background:
- Corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) lack disease-modifying treatments and exhibit significant heterogeneity.
- Neuropathologic processes like alpha-synuclein (αSyn) copathology can impact treatment efficacy.
- Seed amplification assays (SAAs) offer a potential method for detecting such underlying pathologies in vivo.
Purpose of the Study:
- To assess alpha-synuclein (αSyn) copathology in CBS and PSP using cerebrospinal fluid (CSF) αSyn seed amplification assays (αSyn-SAA).
- To evaluate associations between αSyn-SAA positivity and Alzheimer disease (AD) biomarkers, neurodegeneration markers (NfL), and clinical symptoms.
- To investigate the relationship between αSyn-SAA positivity, age at onset, and specific clinical features like REM sleep behavior disorder.
Main Methods:
- Cross-sectional observational study of patients diagnosed with CBS and PSP.
- CSF samples analyzed for αSyn-SAA positivity, AD biomarkers (including Aβ42), and neurofilament light chain (NfL) levels.
- Clinical data collected from medical records to correlate with biomarker findings.
Main Results:
- αSyn-SAA positivity was detected in 35.9% of CBS patients and 28.6% of PSP patients.
- In young-onset patients, αSyn-SAA positivity was associated with Alzheimer disease (AD) positivity (OR 8.8).
- REM sleep behavior disorder was strongly associated with αSyn-SAA positivity (OR 60.2), and an interaction between αSyn-SAA status and age at onset affected Aβ42 levels.
Conclusions:
- The study highlights the utility of αSyn-SAA for in vivo detection of neuropathologic processes in CBS and PSP.
- Results suggest that AD status and older age at onset may be linked to αSyn-SAA positivity.
- These findings offer new avenues for patient stratification in clinical trials for neurodegenerative diseases.
