title: The arsenic exposure hypothesis for Alzheimer disease.
abstract: Prior research has shown that arsenic exposure induces changes that coincide with most of the developmental, biochemical, pathologic, and clinical features of Alzheimer disease (AD) and associated disorders. On the basis of this literature, we propose the Arsenic Exposure Hypothesis for AD that is inclusive of and cooperative with the existing hypotheses. Arsenic toxicity induces hyperphosphorylation of protein tau and overtranscription of the amyloid precursor protein, which are involved in the formation of neurofibrillary tangles and brain amyloid plaques, consistent with the amyloid hypothesis of AD. Arsenic exposure has been associated with cardiovascular diseases and associated risk factors, which is in agreement with the vascular hypothesis of AD. Arsenic exposure invokes brain inflammatory responses, which resonates with the inflammatory hypotheses of AD. Arsenic exposure has been linked to reduced memory and intellectual abilities in children and adolescents, which provides a biologic basis for the developmental origin of health and disease hypothesis for AD. Arsenic and its metabolites generate free radicals causing oxidative stress and neuronal death, which fits the existing oxidative stress hypothesis. Taken together, the arsenic exposure hypothesis for AD provides a parsimonious testable hypothesis for the development and progression of this devastating disease at least for some subsets of individuals.
authors.affiliation: *F. Marie Hall Institute for Rural and Community Health †Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX.The authors declare no financial conflicts of interest.
authors.forename: Gordon
authors.initials: G
authors.lastname: Gong
authors.forename: Sid E
authors.initials: SE
authors.lastname: OʼBryant
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced*; D000818:Animals; D020261:Arsenic Poisoning / Q000150:complications*; D001152:Arsenicals / Q000009:adverse effects; D001921:Brain / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D008569:Memory Disorders / Q000139:chemically induced
chemical_list: D001152:Arsenicals