Dataset Information

APOE DNA methylation is altered in Lewy body dementia.

ABSTRACT: INTRODUCTION:Inheritance of the ?4 allele of apolipoprotein E (APOE) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD. METHODS:Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathological pure (np) controls and npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced. DNA methylation levels of two APOE subregions were then compared for these groups. RESULTS:APOE DNA methylation was significantly reduced in npLBD compared with np controls, and methylation levels were lowest in the LBD + AD group. DISCUSSION:Given that npLBD and npAD postmortem brains shared a similar reduction in APOE methylation, it is possible that an aberrant epigenetic change in APOE is linked to risk for both diseases.

SUBMITTER: Tulloch J

PROVIDER: S-EPMC6050144 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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APOE DNA methylation is altered in Lewy body dementia.

Tulloch Jessica J Leong Lesley L Chen Sunny S Keene C Dirk CD Millard Steven P SP Shutes-David Andrew A Lopez Oscar L OL Kofler Julia J Kaye Jeffrey A JA Woltjer Randy R Nelson Peter T PT Neltner Janna H JH Jicha Gregory A GA Galasko Douglas D Masliah Eliezer E Leverenz James B JB Yu Chang-En CE Tsuang Debby D

Alzheimer's & dementia : the journal of the Alzheimer's Association 20180312 7

<h4>Introduction</h4>Inheritance of the ε4 allele of apolipoprotein E (APOE) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD.<h4>Methods</h4>Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathologic ...[more]

PMID: 29544979

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Project description:BackgroundIndividuals with Lewy body Dementia (LBD), which encompasses both Parkinson disease dementia (PDD) and Dementia with Lewy Bodies (DLB) experience functional decline through Parkinsonism and sedentariness exacerbated by motor, psychiatric and cognitive symptoms. Exercise may improve functional outcomes in Parkinson's disease (PD), and Alzheimer's disease (AD). However, the multi-domain nature of the LBD cluster of symptoms (physical, cognitive, psychiatric, autonomic) results in vulnerable individuals often being excluded from exercise studies evaluating physical function in PD or cognitive function in dementia to avoid confounding results. This review evaluated existing literature reporting the effects of exercise interventions or physical activity (PA) exposure on cluster symptoms in LBD.MethodsA high-sensitivity search was executed across 19 databases. Full-length articles of any language and quality, published or unpublished, that analysed effects of isolated exercise/physical activity on indicative Dementia with Lewy Bodies or PD-dementia cohorts were evaluated for outcomes inclusive of physical, cognitive, psychiatric, physiological and quality of life measures. The protocol for this review (Reg. #: CRD42015019002) is accessible at http://www.crd.york.ac.uk/PROSPERO/.Results111,485 articles were initially retrieved; 288 full articles were reviewed and 89.6% subsequently deemed ineligible due to exclusion of participants with co-existence of dementia and Parkinsonism. Five studies (1 uncontrolled trial, 1 randomized controlled trial and 3 case reports) evaluating 16 participants were included. Interventions were diverse and outcome homogeneity was low. Habitual gait speed outcomes were measured in 13 participants and increased (0.18m/s, 95% CI -0.02, 0.38m/s), exceeding moderate important change (0.14m/s) for PD cohorts. Other outcomes appeared to improve modestly in most participants.DiscussionScarce research investigating exercise in LBD exists. This review confirms exercise studies in PD and dementia consistently exclude LBD participants. Results in this cohort must be treated with caution until robustly designed, larger studies are commissioned to explore exercise efficacy, feasibility and clinical relevance.

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APOE DNA methylation is altered in Lewy body dementia.

Publications

APOE DNA methylation is altered in Lewy body dementia.

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