Plasma biomarkers in dementia with Lewy bodies: evidence from memory clinic settings

Abstract Background Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain. Method We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n=104), Alzheimer’s disease (AD, n=76) and neurological controls (NC, n=27). Measured biomarkers included plasma Aβ ratio, p‐tau181, NfL and GFAP using SIMOA and plasma YKL‐40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n=90) were stratified according to their CSF Aβ profile. Results DLB patients displayed altered plasma Aβ ratio, p‐tau181 and GFAP levels compared with NC and altered plasma Aβ ratio, p‐tau181, GFAP, NfL and sTREM2 levels compared with AD patients (Figure 1, a‐f). Plasma p‐tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC]=0.80) and NC (AUC=0.78) and combining biomarkers did not improve diagnosis performance. Plasma p‐tau181 was the best standalone biomarker to differentiate amyloid‐positive from amyloid‐negative cases (AUC=0.75) and was associated with cognitive status. Combining plasma Aβ ratio, p‐tau181 and NfL increased performance to identify amyloid copathology (AUC=0.79). Principal component analysis identified different segregation patterns of plasma biomarkers in AD and DLB groups (Figure 1, g‐h). Conclusion Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p‐tau181 has potential contribute to identify Aβ copathology in DLB.