A multimodal biomarker strategy to enhance diagnostic precision in neurodegenerative parkinsonism
Summary
Differential diagnosis of neurodegenerative parkinsonian syndromes is complicated by overlapping clinical features and frequent co-pathology that challenges the interpretation of single-protein biomarkers. We evaluated a multimodal, minimally invasive biomarker strategy integrating dermal α-synuclein and 4-repeat tau seed amplification assays (SAAs) with serum neurofilament light chain. In a prospective cohort of 166 participants (Parkinson's disease, n = 40; multiple system atrophy, n = 2
Content
# A multimodal biomarker strategy to enhance diagnostic precision in neurodegenerative parkinsonism
*Published: 2026 May 19*
Differential diagnosis of neurodegenerative parkinsonian syndromes is
complicated by overlapping clinical features and frequent co-pathology that
challenges the interpretation of single-protein biomarkers. We evaluated a
multimodal, minimally invasive biomarker strategy integrating dermal α-synuclein
and 4-repeat tau seed amplification assays (SAAs) with serum neurofilament light
chain. In a prospective cohort of 166 participants (Parkinson's disease, n = 40;
multiple system atrophy, n = 29; progressive supranuclear palsy (PSP), n = 77;
healthy controls, n = 20) with independent external validation (63
participants), α-synuclein SAA identified synucleinopathies with high
sensitivity but was positive in a subset of PSP, which is consistent with
α-synuclein co-pathology. Dermal 4-repeat tau SAA identified PSP with high
sensitivity and specificity. Serum neurofilament light chain distinguished
multiple system atrophy from Parkinson's disease and correlated with disease
severity in PSP. Integrating these complementary biomarkers improved diagnostic
discrimination compared with individual markers and enabled further
stratification within PSP. These findings support a multimodal biomarker
approach for biologically informed diagnosis of parkinsonian syndromes.
DOI: 10.1038/s41591-026-04398-3