Distinctive patterns of DNA methylation associated with Parkinson disease Identification of concordant epigenetic changes in brain and peripheral blood leukocytes

被引:250
作者
Masliah, Eliezer [1 ,2 ]
Dumaop, Wilmar [2 ]
Galasko, Douglas [1 ]
Desplats, Paula [1 ]
机构
[1] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
关键词
DNA methylation; Parkinson disease; brain; peripheral blood leukocytes; epigenetics; neurodegeneration; genome-wide methylation; SUBSTANTIA-NIGRA; GENE-EXPRESSION; ALPHA-SYNUCLEIN; LUNG-CANCER; CELL-DEATH; MECHANISMS; DEMENTIA; MODELS; RISK; PATHWAYS;
D O I
10.4161/epi.25865
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Parkinson disease (PD) is a multifactorial neurodegenerative disorder with high incidence in the elderly, where environmental and genetic factors are involved in etiology. In addition, epigenetic mechanisms, including deregulation of DNA methylation have been recently associated to PD. As accurate diagnosis cannot be achieved pre-mortem, identification of early pathological changes is crucial to enable therapeutic interventions before major neuropathological damage occurs. Here we investigated genome-wide DNA methylation in brain and blood samples from PD patients and observed a distinctive pattern of methylation involving many genes previously associated to PD, therefore supporting the role of epigenetic alterations as a molecular mechanism in neurodegeneration. Importantly, we identified concordant methylation alterations in brain and blood, suggesting that blood might hold promise as a surrogate for brain tissue to detect DNA methylation in PD and as a source for biomarker discovery.
引用
收藏
页码:1030 / 1038
页数:9
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