TY - JOUR
T1 - A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders
AU - Bolsewig, Katharina
AU - Bellomo, Giovanni
AU - Hok-A-Hin, Yanaika S.
AU - Al Idrissi, Imane
AU - Vermunt, Lisa
AU - Lleó, Alberto
AU - Alcolea, Daniel
AU - Sieben, Anne
AU - Engelborghs, Sebastiaan
AU - Simonsen, Anja Hviid
AU - Hasselbalch, Steen G.
AU - Bech, Sara
AU - Morrema, Tjado H.J.
AU - Hoozemans, Jeroen J.M.
AU - Bol, John G.J.M.
AU - van Alphen, Juliette
AU - Gaetani, Lorenzo
AU - Chiasserini, Davide
AU - Paolini Paoletti, Federico
AU - Parnetti, Lucilla
AU - Kang, Sungwoo
AU - Lee, Young Gun
AU - Jeon, Suhee
AU - Lee, Ahreum
AU - Jeon, Seun
AU - Ye, Byoung Seok
AU - del Campo Milán, Marta
AU - van der Flier, Wiesje M.
AU - van de Berg, Wilma D.J.
AU - Lemstra, Afina W.
AU - Willemse, Eline A.J.
AU - Teunissen, Charlotte E.
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/2/16
Y1 - 2026/2/16
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105030248251
U2 - 10.1038/s41591-026-04212-0
DO - 10.1038/s41591-026-04212-0
M3 - Journal article
C2 - 41699128
AN - SCOPUS:105030248251
SN - 1078-8956
JO - Nature Medicine
JF - Nature Medicine
ER -