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.