APOE DNA methylation is altered in Lewy body dementia

Jessica Tulloch; Lesley Leong; Sunny Chen; C. Dirk Keene; Steven P. Millard; Andrew Shutes-David; Oscar L. Lopez; Julia Kofler; Jeffrey A. Kaye; Randy Woltjer; Peter T. Nelson; Janna H. Neltner; Gregory A. Jicha; Douglas Galasko; Eliezer Masliah; James B. Leverenz; Chang En Yu; Debby Tsuang

doi:10.1016/j.jalz.2018.02.005

APOE DNA methylation is altered in Lewy body dementia

Jessica Tulloch, Lesley Leong, Sunny Chen, C. Dirk Keene, Steven P. Millard, Andrew Shutes-David, Oscar L. Lopez, Julia Kofler, Jeffrey A. Kaye, Randy Woltjer, Peter T. Nelson, Janna H. Neltner, Gregory A. Jicha, Douglas Galasko, Eliezer Masliah, James B. Leverenz, Chang En Yu, Debby Tsuang

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English (US)
Pages (from-to)	889-894
Number of pages	6
Journal	Alzheimer's and Dementia
Volume	14
Issue number	7
DOIs	https://doi.org/10.1016/j.jalz.2018.02.005
State	Published - Jul 2018

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

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1016/j.jalz.2018.02.005

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Tulloch, J., Leong, L., Chen, S., Keene, C. D., Millard, S. P., Shutes-David, A., Lopez, O. L., Kofler, J., Kaye, J. A., Woltjer, R., Nelson, P. T., Neltner, J. H., Jicha, G. A., Galasko, D., Masliah, E., Leverenz, J. B., Yu, C. E., & Tsuang, D. (2018). APOE DNA methylation is altered in Lewy body dementia. Alzheimer's and Dementia, 14(7), 889-894. https://doi.org/10.1016/j.jalz.2018.02.005

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title = "APOE DNA methylation is altered in Lewy body dementia",

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.",

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",

author = "Jessica Tulloch and Lesley Leong and Sunny Chen and Keene, {C. Dirk} and Millard, {Steven P.} and Andrew Shutes-David and Lopez, {Oscar L.} and Julia Kofler and Kaye, {Jeffrey A.} and Randy Woltjer and Nelson, {Peter T.} and Neltner, {Janna H.} and Jicha, {Gregory A.} and Douglas Galasko and Eliezer Masliah and Leverenz, {James B.} and Yu, {Chang En} and Debby Tsuang",

note = "Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = jul,

doi = "10.1016/j.jalz.2018.02.005",

language = "English (US)",

volume = "14",

pages = "889--894",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

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TY - JOUR

T1 - APOE DNA methylation is altered in Lewy body dementia

AU - Tulloch, Jessica

AU - Leong, Lesley

AU - Chen, Sunny

AU - Keene, C. Dirk

AU - Millard, Steven P.

AU - Shutes-David, Andrew

AU - Lopez, Oscar L.

AU - Kofler, Julia

AU - Kaye, Jeffrey A.

AU - Woltjer, Randy

AU - Nelson, Peter T.

AU - Neltner, Janna H.

AU - Jicha, Gregory A.

AU - Galasko, Douglas

AU - Masliah, Eliezer

AU - Leverenz, James B.

AU - Yu, Chang En

AU - Tsuang, Debby

PY - 2018/7

Y1 - 2018/7

N2 - 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.

AB - 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.

KW - Alzheimer's disease (AD)

KW - Apolipoprotein E (APOE)

KW - Cerebellum

KW - DNA methylation

KW - Dementia with Lewy bodies (DLB)

KW - Differential methylation

KW - Differentially methylated region (DMR)

KW - Epigenetics

KW - Frontal lobe

KW - Human

KW - Lewy body dementia (LBD)

KW - Postmortem brain

KW - Pyrosequencing

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DO - 10.1016/j.jalz.2018.02.005

M3 - Article

C2 - 29544979

AN - SCOPUS:85044739296

SN - 1552-5260

VL - 14

SP - 889

EP - 894

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 7

ER -

APOE DNA methylation is altered in Lewy body dementia

Abstract

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