title: Does MeCP2 deficiency in autism confer protection against later development of Alzheimer's disease? A reply to Oberman and Pascual-Leone (2014).
abstract: Oberman and Pascual-Leone have proposed a novel hypothesis that the hyperplasticity in autism spectrum disorders (ASD) may confer protection against later development of Alzheimer's disease (AD). The author of this correspondence has made the novel proposition elsewhere that exposure to the increasing agricultural air pollutant, nitrous oxide (N2O), may be the primary etiologic factor in driving neurodevelopmental impairment (i.e., ADHD, ASD, etc.) in humans. This correspondence, therefore, merges these heretofore distinct ideas in order to highlight two mechanisms of how gestational exposure to certain environmental pollutants may confer protection against AD. The hyperplasticity undergirding this protection may include limited noradrenergic discharge from locus coeruleus through MeCP2 deficiency (an emerging biomarker in ASD) and a heightened kappa-opioid receptor (KOR) system. While these endogenous dynamics in ASD may exert neural protection against development of AD, long-term pharmacologic intervention that enhances central catecholaminergic activity may disrupt this benefit, and this may be an important follow-up to address in future studies exploring the novel hypothesis from Oberman and Pascual-Leone.
authors.affiliation: Institute of Health and Environmental Research, Cleveland, OH 44118, USA. Electronic address: keithfluegge@iher.org.
authors.forename: Keith
authors.initials: K
authors.lastname: Fluegge
mesh_terms: D000393:Air Pollutants / Q000032:analysis*; D000397:Air Pollution; D000544:Alzheimer Disease / Q000235:genetics*; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D004781:Environmental Exposure; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000235:genetics; D008962:Models, Theoretical; D009609:Nitrous Oxide / Q000737:chemistry*; D017473:Receptors, Opioid, kappa / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D017473:Receptors, Opioid, kappa; D009609:Nitrous Oxide