Combination Biomarker Testing Enhances Parkinsonism Diagnosis

A prospective study presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders demonstrated that combining assessments of α-synuclein (αSyn) and 4-repeat tau (4R-tau) skin seed amplification assays (SAAs) with serum neurofilament light chain (NfL) levels may enhance stratification and diagnosis across parkinsonian syndromes with high specificity, sensitivity, and agreement with postmortem confirmation. Researchers suggest that this multimodal approach may provide a scalable and minimally invasive tool to enhance diagnostic precision and identify relevant copathologies.

The study cohort included 169 participants (Parkinson disease (PD)=41, multiple system atrophy (MSA)=29, progressive supranuclear palsy (PSP)=79, controls=20). Participants underwent a standardized 3-mm cervical skin biopsy for αSyn and 4R-tau SAAs and a blood draw for serum NfL. Researchers used ROC curve analysis to determine NfL cutoffs that distinguish MSA from PD, with clinical assessments as reference standards and autopsy data from 9 participants for validation.

Key findings from the study include the following:

• αSyn SAAs distinguished synucleinopathies (PD, MSA) from PSP and controls with 87% sensitivity and 76% specificity.
• 4R-tau SAAs identified PSP with 87% sensitivity and 93% specificity.
• Serum NfL differentiated MSA from PD with an area under the curve (AUC) of .94; a 28.8 pg/mL cutoff yielded 100% sensitivity and 93% specificity.
• Biomarker profiles matched autopsy diagnoses in each of the 9 cases confirmed with postmortem validation.
• 22% of PSP cases tested positive for αSyn, a potential copathology linked to shorter disease duration.

Source: Martinez-Valbuena I, Abarghouei M, Olszewska D, et al. A multimodal strategy integrating skin α-synuclein and 4R-tau SAAs with circulating NfL to support the clinical diagnosis of Parkinsonian syndromes. Presented at: International Congress of Parkinson’s Disease and Movement Disorders; October 5–9, 2025; Honolulu, HI.