A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders
Por:
Bolsewig, K, Bellomo, G, Hok-A-Hin, YS, Al Idrissi, I, Vermunt, L, Lleó, A, Alcolea, D, Sieben, A, Engelborghs, S, Simonsen, AH, Hasselbalch, SG, Bech, S, Morrema, THJ, Hoozemans, JJM, Bol, JGJM, Van Alphen, J, Gaetani, L, Chiasserini, D, Paoletti, FP, Parnetti, L, Kang, SW, Lee, YG, Jeon, S, Lee, AH, Jeon, S, Ye, BS, Milán, MD, Van Der Flier, WM, Van De Berg, WDJ, Lemstra, AW, Willemse, EAJ, Teunissen, CE
Publicada:
1 mar 2026
Ahead of Print:
1 feb 2026
Resumen:
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 alpha-synuclein pathology and immunohistochemistry in DLB and PD brain tissue revealed colocalization of DDC and alpha-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.
Filiaciones:
Bolsewig, K:
Amsterdam UMC, Lab Med Dept, Neurochem Lab, Amsterdam Neurosci,VU Univ Med Ctr, Amsterdam, Netherlands
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Bellomo, G:
Univ Perugia, Dept Med & Surg, Sect Neurol, Perugia, Italy
Link Campus Univ, Dept Life Sci Hlth & Hlth Profess, Rome, Italy
Hok-A-Hin, YS:
Amsterdam UMC, Lab Med Dept, Neurochem Lab, Amsterdam Neurosci,VU Univ Med Ctr, Amsterdam, Netherlands
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Al Idrissi, I:
Amsterdam UMC, Lab Med Dept, Neurochem Lab, Amsterdam Neurosci,VU Univ Med Ctr, Amsterdam, Netherlands
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Vermunt, L:
Amsterdam UMC, Lab Med Dept, Neurochem Lab, Amsterdam Neurosci,VU Univ Med Ctr, Amsterdam, Netherlands
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Univ Amsterdam, Amsterdam Alzheimer Ctr, Med Ctr, Amsterdam, Netherlands
Lleó, A:
Univ Autonoma Barcelona, Hosp St Pau, Hosp Santa Creu & St Pau, Inst Invest Biomed St Pau IIB ST PAU, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Hosp St Pau, Hosp Santa Creu & St Pau, Inst Invest Biomed St Pau IIB ST PAU, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Madrid, Spain
Sieben, A:
Born Bunge Inst, Neuropathol lab, IBB NeuroBiobank, BB1901113, Antwerp, Belgium
Antwerp Univ Hosp UZA, Dept Pathol, Antwerp, Belgium
Univ Antwerp, Fac Med & Hlth Sci, Lab Neurol Translat Neurosci, Antwerp, Belgium
Engelborghs, S:
Univ Antwerp, Inst Born Bunge, Reference Ctr Biol Markers Dementia BIODEM, Lab Neurochem & Behav, Antwerp, Belgium
Vrije Univ Brussel, Ctr Neurosci C4N, Neuroprotect & Neuromodulat Res Grp NEUR, Brussels, Belgium
Univ Ziekenhuis Brussel, Dept Neurol, Brussels, Belgium
Simonsen, AH:
Univ Copenhagen, Danish Dementia Res Ctr, Rigshosp, Copenhagen, Denmark
Hasselbalch, SG:
Univ Copenhagen, Danish Dementia Res Ctr, Rigshosp, Copenhagen, Denmark
Bech, S:
Copenhagen Univ Hosp, Bispebjerg & Frederiksberg Hosp, Dept Neurol, Copenhagen, Denmark
Morrema, THJ:
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Amsterdam UMC, Amsterdam Neurosci, Dept Pathol, Amsterdam, Netherlands
Hoozemans, JJM:
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Amsterdam UMC, Amsterdam Neurosci, Dept Pathol, Amsterdam, Netherlands
Bol, JGJM:
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Vrije Univ, Dept Anat & Neurosci, Sect Clin Neuroanat & Biobanking, Amsterdam UMC, Amsterdam, Netherlands
Van Alphen, J:
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Univ Amsterdam, Amsterdam Alzheimer Ctr, Med Ctr, Amsterdam, Netherlands
Gaetani, L:
Univ Perugia, Dept Med & Surg, Sect Neurol, Perugia, Italy
Chiasserini, D:
Univ Perugia, Dept Med & Surg, Sect Neurol, Perugia, Italy
Paoletti, FP:
Univ Perugia, Dept Med & Surg, Sect Neurol, Perugia, Italy
Parnetti, L:
Univ Perugia, Dept Med & Surg, Sect Neurol, Perugia, Italy
Kang, SW:
Hanyang Univ, Hanyang Seoul Hosp, Dept Neurol, Coll Med, Seoul, South Korea
Lee, YG:
Inje Univ, Coll Med, Ilsan Paik Hosp, Dept Neurol, Goyang, South Korea
Jeon, S:
Yonsei Univ, Coll Med, Metab Dementia Res Inst, Seoul, South Korea
Lee, AH:
Yonsei Univ, Coll Med, Metab Dementia Res Inst, Seoul, South Korea
Jeon, S:
Yonsei Univ, Coll Med, Metab Dementia Res Inst, Seoul, South Korea
Ye, BS:
Yonsei Univ, Coll Med, Dept Neurol, Seoul, South Korea
Milán, MD:
Pasqual Maragall Fdn, Barcelonasseta Brain Res Ctr, Barcelona, Spain
Hosp del Mar Res Inst IMIM, Barcelona, Spain
Van Der Flier, WM:
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Vrije Univ Amsterdam, Epidemiol & Data Sci, Amsterdam UMC locat VUmc, Amsterdam, Netherlands
Alzheimer Nederland, Amersfoort, Netherlands
Amsterdam Publ Hlth, Amsterdam, Netherlands
Van De Berg, WDJ:
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Vrije Univ, Dept Anat & Neurosci, Sect Clin Neuroanat & Biobanking, Amsterdam UMC, Amsterdam, Netherlands
Lemstra, AW:
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Univ Amsterdam, Amsterdam Alzheimer Ctr, Med Ctr, Amsterdam, Netherlands
Willemse, EAJ:
Amsterdam UMC, Lab Med Dept, Neurochem Lab, Amsterdam Neurosci,VU Univ Med Ctr, Amsterdam, Netherlands
Univ Basel, Multiple Sclerosis Ctr, Dept Neurol, Basel, Switzerland
Univ Hosp Basel, Res Ctr Clin Neuroimmunol & Neurosci Basel, Dept Biomed, Basel, Switzerland
Univ Hosp Basel, Clin Res, Basel, Switzerland
Univ Basel, Basel, Switzerland
Teunissen, CE:
Amsterdam UMC, Lab Med Dept, Neurochem Lab, Amsterdam Neurosci,VU Univ Med Ctr, Amsterdam, Netherlands
Amsterdam UMC, Neurodegenerat program, Amsterdam Neurosci, Amsterdam, Netherlands
Green Submitted, hybrid
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