A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders
Summary
Accurate diagnosis of dementia with Lewy bodies (DLB) remains challenging, with misdiagnosis potentially leading to harmful treatment decisions. DOPA decarboxylase (DDC) shows promise as a cerebrospinal fluid (CSF) biomarker for DLB and Parkinson's disease (PD), but quantitative assays are needed for its clinical implementation. Here we report on the development of two DDC immunoassays and the extensive clinical validation of DDC across three clinical cohorts (n = 740), one biologically de
Content
# A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders
*Published: 2026 Mar*
Accurate diagnosis of dementia with Lewy bodies (DLB) remains challenging, with
misdiagnosis potentially leading to harmful treatment decisions. DOPA
decarboxylase (DDC) shows promise as a cerebrospinal fluid (CSF) biomarker for
DLB and Parkinson's disease (PD), but quantitative assays are needed for its
clinical implementation. Here we report on the development of two DDC
immunoassays and the extensive clinical validation of DDC across three clinical
cohorts (n = 740), one biologically defined cohort (n = 253), one cohort with
detailed dopamine transporter imaging information (n = 102) and one
autopsy-confirmed cohort (n = 78). CSF DDC levels were significantly higher in
DLB and PD (up to 2.5-fold versus controls; 1.9-fold versus AD), showing area
under the curve values > 0.9 for differential diagnosis. Elevated CSF DDC was
linked to the presence, but not severity, of motor impairment. In
autopsy-confirmed DLB, higher CSF DDC correlated with progressing α-synuclein
pathology and immunohistochemistry in DLB and PD brain tissue revealed
colocalization of DDC and α-synuclein in the substantia nigra. These findings
underscore DDC's value to support DLB and PD diagnosis, paving the way for its
clinical implementation using the here-presented developed immunoassays.
DOI: 10.1038/s41591-026-04212-0