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      APOE DNA methylation is altered in Lewy body dementia

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          Abstract

          INTRODUCTION

          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 brain (PMB) prompted this study to investigate APOE methylation in LBD.

          METHODS

          Genomic DNA from PMB tissues (frontal lobe and cerebellum) of neuropathological pure (np) Controls, 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 to npControls, and methylation levels were lowest in the LBD + AD group.

          DISCUSSION

          Given that npLBD and npAD PMB shared a similar reduction in APOE methylation, it is possible that an aberrant epigenetic change in APOE is linked to risk for both diseases.

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          Author and article information

          Journal
          101231978
          33173
          Alzheimers Dement
          Alzheimers Dement
          Alzheimer's & dementia : the journal of the Alzheimer's Association
          1552-5260
          1552-5279
          23 May 2018
          12 March 2018
          July 2018
          01 July 2019
          : 14
          : 7
          : 889-894
          Affiliations
          [1 ]Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, 98108, USA ; Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA, 98195, USA
          [2 ]Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA, 98195, USA
          [3 ]Department of Pathology, Neuropathology Division, University of Washington, Seattle, WA, 98195, USA
          [4 ]Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, 98108, USA
          [5 ]Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, 98108, USA; Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, 98108, USA
          [6 ]Department of Neurology, University of Pittsburgh, Pittsburgh, PA, 15213, USA
          [7 ]Department of Pathology, Division of Neuropathology, University of Pittsburgh, Pittsburgh, PA, 15261, USA
          [8 ]Department of Neurology, Oregon Health and Science University, Portland, OR, 97239, USA
          [9 ]Department of Pathology, Oregon Health and Science University, Portland, OR, 97239, USA
          [10 ]Department of Pathology, University of Kentucky, Lexington, KY, 40536, USA
          [11 ]Department of Neurology, University of Kentucky, Lexington, KY, 40536, USA
          [12 ]Department of Neurosciences, University of California San Diego, San Diego CA, 92093, USA
          [13 ]National Institutes of Health, National Institute on Aging, Division of Neuroscience, Bethesda, MD, 20892, USA
          [14 ]Department of Neurology, Cleveland Clinic, Cleveland, OH, 44195, USA
          [15 ]Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, 98108, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA
          Author notes
          [* ]Corresponding author. Address: 1660 S Columbian Way, Box #358280, Seattle, WA 98108; jforaker@ 123456uw.edu ; Phone: 206-277-6200
          Article
          PMC6050144 PMC6050144 6050144 nihpa958294
          10.1016/j.jalz.2018.02.005
          6050144
          29544979
          b55bde43-0d45-4ccc-a558-b6c5a9fbca8f
          History
          Categories
          Article

          human,differential methylation,apolipoprotein E (APOE),pyrosequencing,differentially methylated region (DMR),postmortem brain,Alzheimer’s disease (AD),Lewy body dementia (LBD),cerebellum,dementia with Lewy bodies (DLB),epigenetics,frontal lobe,DNA methylation

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