Jessica Tulloch1, Lesley Leong2, Sunny Chen2, C Dirk Keene3, Steven P Millard4, Andrew Shutes-David5, Oscar L Lopez6, Julia Kofler7, Jeffrey A Kaye8, Randy Woltjer9, Peter T Nelson10, Janna H Neltner10, Gregory A Jicha11, Douglas Galasko12, Eliezer Masliah13, James B Leverenz14, Chang-En Yu15, Debby Tsuang16. 1. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: jforaker@uw.edu. 2. Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA. 3. Neuropathology Division, Department of Pathology, University of Washington, Seattle, WA, USA. 4. Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA. 5. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA. 6. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA. 7. Division of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. 8. Department of Neurology, Oregon Health and Science University, Portland, OR, USA. 9. Department of Pathology, Oregon Health and Science University, Portland, OR, USA. 10. Department of Pathology, University of Kentucky, Lexington, KY, USA. 11. Department of Neurology, University of Kentucky, Lexington, KY, USA. 12. Department of Neurosciences, University of California San Diego, San Diego CA, USA. 13. National Institutes of Health, Division of Neuroscience, National Institute on Aging, Bethesda, MD, USA. 14. Department of Neurology, Cleveland Clinic, Cleveland, OH, USA. 15. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA. 16. Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
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 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. Published by Elsevier Inc.
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 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. Published by Elsevier Inc.
Entities:
Keywords:
Alzheimer's disease (AD); Apolipoprotein E (APOE); Cerebellum; DNA methylation; Dementia with Lewy bodies (DLB); Differential methylation; Differentially methylated region (DMR); Epigenetics; Frontal lobe; Human; Lewy body dementia (LBD); Postmortem brain; Pyrosequencing
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