title: Heroin abuse exaggerates age-related deposition of hyperphosphorylated tau and p62-positive inclusions.
abstract: The observation of increased hyperphosphorylated tau levels correlating with microglial activation in opiate abusers has been interpreted as predisposition to accelerated Alzheimer disease-related changes. The present study focused on evaluating additional neurodegeneration-related proteins, including α-synuclein and TDP-43, and p62-positive deposits. We performed a systematic mapping of protein deposits in the brains of 27 individuals with documented heroin addiction (age: 19-40 years) and compared with 11 controls (age: 15-40 years). We confirm previous findings that heroin addiction associates with tau hyperphosphorylation in predilection brain areas for aging and Alzheimer disease. Furthermore, we show that this occurs also in areas implicated in the molecular disturbances and in vivo neuronal networks related to heroin abuse. There was, however, no presence of amyloid-beta deposits. We extend previous findings by showing the lack of TDP-43 or α-synuclein pathology and emphasize the independent effect of the duration of drug use on the appearance of age-related p62-positive neuritic profiles. These observations provide unique insights about neuropathological alterations in the brains of young heroin addicts and have implications about brain aging and the influences of environmental and toxic factors.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria; Neuropathology and Prion Disease Reference Center, Semmelweis University, Budapest, Hungary. Electronic address: gabor.kovacs@meduniwien.ac.at.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Department of Forensic Medicine, National Board of Forensic Medicine, Uppsala University, Uppsala, Sweden.
authors.forename: Monika Cs
authors.initials: MC
authors.lastname: Horvath
authors.affiliation: Neuropathology and Prion Disease Reference Center, Semmelweis University, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Majtenyi
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Mirjam I
authors.initials: MI
authors.lastname: Lutz
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Yasmin L
authors.initials: YL
authors.lastname: Hurd
authors.affiliation: Department of Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary. Electronic address: evakeller690@yahoo.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Keller
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006556:Heroin Dependence / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism*; D055815:Young Adult; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Aging; Heroin; Neuropathology; Opiate; TDP-43; Tau; p62; α-Synuclein