Diagnosis of dementia with Lewy bodies (DLB) is challenging and specific biofluid biomarkers are highly needed. This study used proximity extension-based assays to measure 665 proteins in cerebrospinal fluid (CSF) from patients with DLB, Alzheimer's disease (AD), and controls. Over 50 CSF proteins were dysregulated in DLB, many related to myelination. Dopa decarboxylase (DDC) was the strongest dysregulated protein, effectively discriminating DLB from controls and AD. A 7-CSF biomarker panel further improved DLB/AD discrimination. A custom multiplex panel was validated in independent cohorts, including an autopsy-confirmed cohort. This study identifies DLB-specific protein changes and provides a practical biomarker panel for accurate DLB identification.

Marta del Campo, Lisa Vermunt, Carel F. W. Peeters, Anne Sieben, Yanaika S. Hok-A-Hin, Alberto Lleó, Daniel Alcolea, Mirrelijn van Nee, Sebastiaan Engelborghs, Juliette L. van Alphen, Sanaz Arezoumandan, Alice Chen-Plotkin, David J. Irwin, Wiesje M. van der Flier, Afina W. Lemstra, Charlotte E. Teunissen