路易体痴呆症患者血液中DNA甲基化的差异
Differential blood DNA methylation across Lewy body dementias.
作者信息
Nasamran Chanond A, Sachan Anubhav Nikunj Singh, Mott Jennifer, Kuras Yuliya I, Scherzer Clemens R, Study Harvard Biomarkers, Ricciardelli Eugenia, Jepsen Kristen, Edland Steven D, Fisch Kathleen M, Desplats Paula
机构信息
Center for Computational Biology & Bioinformatics Department of Medicine University of California San Diego La Jolla California USA.
Division of Biostatistics, Department of Family Medicine and Public Health University of California San Diego La Jolla California USA.
出版信息
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.
引言
路易体痴呆（DLB）和帕金森病痴呆（PDD）的特征为认知改变、视幻觉和运动障碍。诊断基于临床表现的类型和时间；然而，确定临床亚型具有挑战性。血液DNA甲基化作为路易体疾病（LBD）生物标志物的效用大多未被探索。
方法
我们对42例DLB和50例PDD病例的血液甲基化进行了横断面分析，应用线性模型比较组间差异，并使用逻辑最小绝对收缩和选择算子回归来探索甲基化信号的判别能力。
结果
与PDD相比，DLB血液显示出差异甲基化。一些甲基化变化与LBD的核心特征相关。探针集对区分不同变体具有较高的预测价值。
讨论
我们的研究首次探索了LBD血液甲基化。尽管临床表现存在重叠，但我们检测到了差异表观遗传特征，若能在独立队列中得到证实，可能会开发出有用的生物标志物。
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