MGMT, a risk factor for both genetic and environmental forms of dementia

Glen E. Kisby; Heaton Oakes; David Beckett; Peter S. Spencer

doi:10.1002/alz.12900

MGMT, a risk factor for both genetic and environmental forms of dementia

Glen E. Kisby, Heaton Oakes, David Beckett, Peter S. Spencer

Neurology

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

1 Scopus citations

Abstract

MGMT, the gene coding for the DNA-repair protein O⁶-methylguanine methyltransferase, which has been recently shown to be a risk factor for inherited forms of Alzheimer's disease (AD), notably among women, might also be linked to Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC), one phenotype of which is an AD-like dementia. Guam ALS/PDC is strongly considered to be an environmental disorder caused by oral exposure to natural toxins (i.e., genotoxic/epigenotoxic chemicals), notably methylazoxymethanol (MAM) that alkylates guanine to form O⁶-methylguanine, found in the seed of cycad plants traditionally used for food. Thus, the DNA-repair protein MGMT might participate in both AD and in the AD-related disorder ALS/PDC.

Original language	English (US)
Journal	Alzheimer's and Dementia
DOIs	https://doi.org/10.1002/alz.12900
State	Accepted/In press - 2022

ASJC Scopus subject areas

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

Access to Document

10.1002/alz.12900

Cite this

@article{54387952f8df41719c1b17b9c1dd4b85,

title = "MGMT, a risk factor for both genetic and environmental forms of dementia",

abstract = "MGMT, the gene coding for the DNA-repair protein O6-methylguanine methyltransferase, which has been recently shown to be a risk factor for inherited forms of Alzheimer's disease (AD), notably among women, might also be linked to Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC), one phenotype of which is an AD-like dementia. Guam ALS/PDC is strongly considered to be an environmental disorder caused by oral exposure to natural toxins (i.e., genotoxic/epigenotoxic chemicals), notably methylazoxymethanol (MAM) that alkylates guanine to form O6-methylguanine, found in the seed of cycad plants traditionally used for food. Thus, the DNA-repair protein MGMT might participate in both AD and in the AD-related disorder ALS/PDC.",

author = "Kisby, {Glen E.} and Heaton Oakes and David Beckett and Spencer, {Peter S.}",

note = "Funding Information: We thank Michael Pollanen, MD, PhD (University of Toronto) for providing brain tissue from Guam cases of ALS/PDC and Randy Woltjer, MD, PhD (Oregon Brain Bank, OHSU) for brain tissue sections (control, AD, and Guam cases) for immunohistochemistry. G.K.{\textquoteright}s team is supported by Western University of Health Sciences. P.S. is supported by NIH grant R21NS108355. Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2022",

doi = "10.1002/alz.12900",

language = "English (US)",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - MGMT, a risk factor for both genetic and environmental forms of dementia

AU - Kisby, Glen E.

AU - Oakes, Heaton

AU - Beckett, David

AU - Spencer, Peter S.

N1 - Funding Information: We thank Michael Pollanen, MD, PhD (University of Toronto) for providing brain tissue from Guam cases of ALS/PDC and Randy Woltjer, MD, PhD (Oregon Brain Bank, OHSU) for brain tissue sections (control, AD, and Guam cases) for immunohistochemistry. G.K.’s team is supported by Western University of Health Sciences. P.S. is supported by NIH grant R21NS108355. Publisher Copyright: © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PY - 2022

Y1 - 2022

N2 - MGMT, the gene coding for the DNA-repair protein O6-methylguanine methyltransferase, which has been recently shown to be a risk factor for inherited forms of Alzheimer's disease (AD), notably among women, might also be linked to Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC), one phenotype of which is an AD-like dementia. Guam ALS/PDC is strongly considered to be an environmental disorder caused by oral exposure to natural toxins (i.e., genotoxic/epigenotoxic chemicals), notably methylazoxymethanol (MAM) that alkylates guanine to form O6-methylguanine, found in the seed of cycad plants traditionally used for food. Thus, the DNA-repair protein MGMT might participate in both AD and in the AD-related disorder ALS/PDC.

AB - MGMT, the gene coding for the DNA-repair protein O6-methylguanine methyltransferase, which has been recently shown to be a risk factor for inherited forms of Alzheimer's disease (AD), notably among women, might also be linked to Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC), one phenotype of which is an AD-like dementia. Guam ALS/PDC is strongly considered to be an environmental disorder caused by oral exposure to natural toxins (i.e., genotoxic/epigenotoxic chemicals), notably methylazoxymethanol (MAM) that alkylates guanine to form O6-methylguanine, found in the seed of cycad plants traditionally used for food. Thus, the DNA-repair protein MGMT might participate in both AD and in the AD-related disorder ALS/PDC.

UR - http://www.scopus.com/inward/record.url?scp=85145305515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85145305515&partnerID=8YFLogxK

U2 - 10.1002/alz.12900

DO - 10.1002/alz.12900

M3 - Letter

C2 - 36583449

AN - SCOPUS:85145305515

SN - 1552-5260

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

ER -

MGMT, a risk factor for both genetic and environmental forms of dementia

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this