Differential blood dna methylation across lewy body dementias

Abstract

Introduction: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are characterized by cognitive alterations, visual hallucinations, and motor impairment. Diagnosis is based on type and timing of clinical manifestations; however, determination of clinical subtypes is challenging. The utility of blood DNA methylation as a biomarker for Lewy body disorders (LBD) is mostly unexplored. Methods: We performed a cross-sectional analysis of blood methylation in 42 DLB and 50 PDD cases applying linear models to compare groups and logistic least abso-lute shrinkage and selection operator regression to explore the discriminant power of methylation signals. Results: DLB blood shows differential methylation compared to PDD. Some methyla-tion changes associate with core features of LBD. Sets of probes show high predictive value to discriminate between variants. Discussion: Our study is the first to explore LBD blood methylation. Despite overlap-ping clinical presentation, we detected differential epigenetic signatures that, if con-firmed in independent cohorts, could be developed into useful biomarkers.