A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders.
СтатьяНазвание и аннотация: Перевод в очереди
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Bolsewig Katharina, Bellomo Giovanni, Hok-A-Hin Yanaika S, Al Idrissi Imane, Vermunt Lisa, Lleó Alberto, Alcolea Daniel, Sieben Anne, Engelborghs Sebastiaan, Simonsen Anja Hviid, Hasselbalch Steen G, Bech Sara, Morrema Tjado H J, Hoozemans Jeroen J M, Bol John G J M, van Alphen Juliette, Gaetani Lorenzo, Chiasserini Davide, Paolini Paoletti Federico, Parnetti Lucilla, Kang Sungwoo, Lee Young-Gun, Jeon Suhee, Lee Ahreum, Jeon Seun, Ye Byoung Seok, Del Campo Milán Marta, van der Flier Wiesje M, van de Berg Wilma D J, Lemstra Afina W, Willemse Eline A J, Teunissen Charlotte E
Аннотация
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.