Differential blood DNA methylation across Lewy body dementias

Alzheimers Dement (Amst). 2021 Feb 20;13(1):e12156. doi: 10.1002/dad2.12156. eCollection 2021.


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 absolute shrinkage and selection operator regression to explore the discriminant power of methylation signals.

Results: DLB blood shows differential methylation compared to PDD. Some methylation 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 overlapping clinical presentation, we detected differential epigenetic signatures that, if confirmed in independent cohorts, could be developed into useful biomarkers.

Keywords: DNA methylation; Lewy body diseases (LBD); Parkinson's disease dementia (PDD); REM sleep behavior disorder (RBD); biomarker; blood; cognitive scores; dementia; dementia with Lewy bodies (DLB); epigenetics.