Abstract
Background: Lifetime exposure to environmental (neuro) toxicants may contribute to the pathogenesis of Alzheimer’s Disease (AD). Since many contaminants do not cross the blood-brain barrier, brain tissue alone cannot serve to assess the spectrum of environmental exposures.
Methods: We used liquid and gas chromatography tandem mass spectrometry to monitor, in postmortem liver and adipose tissues of AD patients and age-matched controls, the occurrence and concentrations of 11 environmental contaminants.
Results: Seven toxicants were detected at 100% frequency: p,p'-DDE, dieldrin, triclosan, methylparaben, bisphenol A, fipronil and tetrabromobisphenol A (TBBPA). Intra-individual, tissuedependent differences were detected for triclosan, methylparaben, fipronil and TBBPA. High concentrations of p,p’-DDE and dieldrin were observed in adipose tissue when compared to liver values for both AD cases and controls.
Conclusion: This study provides vital data on organ-specific human body burdens to select analytes and demonstrate the feasibility of analyzing small sample quantities for toxicants suspected to constitute AD risk factors.
Keywords: Alzheimer's disease, environmental (neuro) toxicants, pollutants, contaminants, liquid and gas chromatography tandem mass spectrometry, liver, adipose tissue.
[1]
Yegambaram M, Manivannan B, Beach TG, Halden RU. Role of environmental contaminants in the etiology of alzheimer’s disease: a review. Curr Alzheimer Res 12(2): 116-46.(2015);
[2]
Copley SD. Evolution of efficient pathways for degradation of anthropogenic chemicals. Nat Chem Biol 5(8): 559-66.(2009);
[3]
Baldi I, Lebailly P, Mohammed-Brahim B, Letenneur L, Dartigues J-F, Brochard P. Neurodegenerative diseases and exposure to pesticides in the elderly. Am J Epidemiol 157(5): 409-14.(2003);
[4]
Alzheimer’s-Association. Alzheimer’s Disease Facts and Figures. Alzheimers Dement 14(3): 367-429.(2018);
[5]
Lahiri DK, Maloney B, Zawia NH. The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry 14(11): 992-1003.(2009);
[6]
Basha MR, Wei W, Bakheet SA, Benitez N, Siddiqi HK, Ge Y-W, et al. The Fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and β-amyloid in the aging brain. J Neurosci 25(4): 823-9.(2005);
[7]
Bakulski KM, Rozek LS, Dolinoy DC, Paulson HL, Hu H. Alzheimer’s disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics. Curr Alzheimer Res 9(5): 563-73.(2012);
[8]
Maloney B, Lahiri DK. Epigenetics of dementia: understanding the disease as a transformation rather than a state. Lancet Neurol 15(7): 760-74.(2016);
[9]
Zenaro E, Piacentino G, Constantin G. The blood-brain barrier in Alzheimer’s disease. Neurobiol Dis 107: 41-56.(2017);
[10]
Chakraborty A, de Wit NM, van der Flier WM, de Vries HE. The blood brain barrier in Alzheimer’s disease. Vascul Pharmacol 89: 12-8.(2017);
[11]
Dewailly E, Mulvad G, Pedersen HS, Ayotte P, Demers A, Weber JP, et al. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland. Environ Health Perspect 107(10): 823-8.(1999);
[12]
de Vlieger M, Robinson J, Baldwin MK, Crabtree AN, van Dijk MC. The organochlorine insecticide content of human tissues. Arch Environ Health. An Intern J 17(5): 759-67.(1968);
[13]
van der Meer TP, Artacho-Cordón F, Swaab DF, Struik D, Makris KC, Wolffenbuttel BHR, et al. Distribution of non-persistent endocrine disruptors in two different regions of the human brain. Int J Environ Res Public Health 14(9): 1059.(2017);
[14]
Chhillar N, Singh NK, Banerjee BD, Bala K, Sharma D, Mustafa M, et al. β-hexachlorocyclohexane as a risk for Alzheimer’s disease: a pilot study in north indian population. Am J Alzheimers Dis 1: 60-71.(2013);
[15]
Richardson JR, Roy A, Shalat SL, von Stein RT, Hossain MM, Buckley B, et al. Elevated serum pesticide levels and risk for alzheimer disease. JAMA Neurol 71(3): 284-90.(2014);
[16]
Cam M, Durieu E, Bodin M, Manousopoulou A, Koslowski S, Vasylieva N, et al. Induction of amyloid-β42 production by fipronil and other pyrazole insecticides. J Alzheimers Dis 62(4): 1663-81.(2018);
[17]
de Wit CA. An overview of brominated flame retardants in the environment. Chemosphere 46(5): 583-624.(2002);
[18]
Halden RU. On the need and speed of regulating triclosan and triclocarban in the United States. Environ Sci Technol 48(7): 3603-11.(2014);
[19]
Abbas S, Greige-Gerges H, Karam N, Piet M-H, Netter P, Magdalou J. Metabolism of Parabens (4-Hydroxybenzoic Acid Esters) by Hepatic Esterases and UDP-Glucuronosyltransferases in Man. Drug Metab Pharmacokinet 25(6): 568-77.(2010);
[20]
Barse AV, Chakrabarti T, Ghosh TK, Pal AK, Kumar N, Raman RP, et al. Vitellogenin induction and histo-metabolic changes following exposure of cyprinus carpio to methyl paraben. Asian-Aus J Ani Sci 23(12): 1557-65.(2010);
[21]
Kim AH, Chun HJ, Lee S, Kim HS, Lee J. High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention. Food Chem Toxicol 106: 223-31.(2017);
[22]
Sun Y, Nakashima MN, Takahashi M, Kuroda N, Nakashima K. Determination of bisphenol A in rat brain by microdialysis and column switching high-performance liquid chromatography with fluorescence detection. Biomed Chrom 16(5): 319-26.(2002);
[23]
Lee S, Mulay P, Diebolt-Brown B, Lackovic M, Mehler L, Beckman J, et al. Acute illnesses associated with exposure to fipronil—surveillance data from 11 states in the United States, 2001–2007. Clin Toxicol 48(7): 737-44.(2010);
[24]
Dang VD, Kroll KJ, Supowit SD, Halden RU, Denslow ND. Tissue distribution of organochlorine pesticides in largemouth bass (Micropterus salmoides) from laboratory exposure and a contaminated lake. Environ Pollut 216: 877-83.(2016);
[25]
USDHHS ToxicologicaL Profile for DDT, DDE, and DDD. In: Public Health Service Atlanta: Agency for Toxic Substances and
Disease Registry. 1-497.(2002);
[26]
Beach TG, Sue LI, Walker DG, Roher AE, Lue L, Vedders L, et al. The sun health research institute brain donation program: description and eexperience, 1987-2007. Cell Tissue Bank 9(3): 229-45.(2008);
[27]
Beach TG, Adler CH, Sue LI, Serrano G, Shill HA, Walker DG, et al. Arizona study of aging and neurodegenerative disorders and brain and body donation program. Neuropathology 35(4): 354-89.(2015);
[28]
The National Institute on Aging. Group RIW. Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. Neurobiol Aging 18(4)(Suppl. 1): S1-2.(1997);
[29]
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4): 239-59.(1991);
[30]
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to establish a registry for Alzheimer’s disease (CERAD). Part ii standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41(4): 479-86.(1991);
[31]
Pycke BFG, Geer LA, Dalloul M, Abulafia O, Halden RU. Maternal and fetal exposure to parabens in a multiethnic urban U.S. population. Environ Int 84: 193-200.(2015);
[32]
Pycke BFG, Geer LA, Dalloul M, Abulafia O, Jenck AM, Halden RU. Human fetal exposure to triclosan and triclocarban in an urban population from Brooklyn, New York. Environ Sci Technol 48(15): 8831-8.(2014);
[33]
Supowit S. Methods and devices for assessment of fiprole pesticides in engineered waterways Doctor of Philosophy. Tempe: Arizona State University (2015).
[34]
Beyer WN, Gale RW. Persistence and changes in bioavailability of dieldrin, DDE, and heptachlor epoxide in earthworms over 45 years. Ambio 42(1): 83-9.(2013);
[35]
Geens T, Roosens L, Neels H, Covaci A. Assessment of human exposure to bisphenol-A, triclosan and tetrabromobisphenol-A through indoor dust intake in Belgium. Chemosphere 76(6): 755-60.(2009);
[36]
Ruszkiewicz JA, Li S, Rodriguez MB, Aschner M. Is Triclosan a neurotoxic agent? J Toxicol Environ Health. Part B 20(2): 104-17.(2017);
[37]
Geens T, Neels H, Covaci A. Distribution of bisphenol-A, triclosan and n-nonylphenol in human adipose tissue, liver and brain. Chemosphere 87: 796-802.(2012);
[39]
Barr L, Metaxas G, Harbach CAJ, Savoy LA, Darbre PD. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum. J Appl Toxicol 32(3): 219-32.(2012);
[40]
Johnson-Restrepo B, Adams DH, Kannan K, Tetrabromobisphenol A. TBBPA) and hexabromocyclododecanes (HBCDs) in tissues of humans, dolphins, and sharks from the United States. Chemosphere 70(11): 1935-44.(2008);
[41]
Carignan CC, Abdallah MA-E, Wu N, Heiger-Bernays W, McClean MD, Harrad S, et al. Predictors of tetrabromobisphenol-A (TBBP-A) and hexabromocyclododecanes (HBCD) in milk from boston mothers. Environ Sci Technol 46(21): 12146-53.(2012);
[42]
Nahar MS, Liao C, Kannan K, Harris C, Dolinoy DC. In utero bisphenol a concentration, metabolism, and global DNA methylation across matched placenta, kidney, and liver in the human fetus. Chemosphere 124: 54-60.(2015);
[43]
Wang L, Asimakopoulos AG, Kannan K. Accumulation of 19 environmental phenolic and xenobiotic heterocyclic aromatic compounds in human adipose tissue. Environ Int 78: 45-50.(2015);
[44]
Artacho-Cordón F, Arrebola JP, Nielsen O, Hernández P, Skakkebaek NE, Fernández MF, et al. Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum. Environ Res 156: 120-7.(2017);
[45]
Fernandez MF, Arrebola JP, Taoufiki J, Navalón A, Ballesteros O, Pulgar R, et al. Bisphenol-A and chlorinated derivatives in adipose tissue of women. Reprod Toxicol 24(2): 259-64.(2007);
[46]
Wang T, Xie C, Yu P, Fang F, Zhu J, Cheng J, et al. Involvement of insulin signaling disturbances in bisphenol A-induced Alzheimer’s disease-like neurotoxicity. Sci Rep 7(1): 7497-97.(2017);
[47]
Magalhães JZ, Sandini TM, Udo MSB, Fukushima AR, Spinosa H. de S. Fipronil: uses, pharmacological and toxicological features. Rep 1: 67-83.(2018);
[48]
Tonnelier A, Coecke S, Zaldívar J-M. Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model. Arch Toxicol 86(3): 393-403.(2012);
[49]
Szymczynski GA, Waliszewski SM. Comparison of the content of chlorinated pesticide residues in human semen, testicles and fat tissues. Andrologia 13(3): 250-2.(1981);
[50]
Singh N, Chhillar N, Banerjee B, Bala K, Basu M, Mustafa M. Organochlorine pesticide levels and risk of Alzheimer’s disease in north Indian population. Hum Exp Toxicol 32(1): 24-30.(2013);
[51]
Jaga K, Dharmani C. Global surveillance of DDT and DDE levels in human tissues. Int J Occup Med Environ Health 16(1): 7-20.(2003);
[52]
Ahmad N, Harsas W, Marolt RS, Morton M, Pollack JK. Total DDT and dieldrin content of human adipose tissue. Bulletin of
Environmental Contamination and Toxicology 41(4): 802-8.(1988);
[53]
B Ackerman L. Overview of human exposure to dieldrin residues
in the environment and current trends of residue levels in tissue (1980).
[54]
Jorgenson JL. Aldrin and dieldrin: a review of research on their production, environmental deposition and fate, bioaccumulation, toxicology, and epidemiology in the United States. Environ Health Perspect 109(Suppl. 1): 113-39.(2001);
[55]
Kanthasamy AG, Kitazawa M, Kanthasamy A, Anantharam V. Dieldrin-induced neurotoxicity: relevance to parkinson’s disease pathogenesis. Neurotoxicology 26(4): 701-19.(2005);
[56]
Savković-Stevanović J. Xenobiotics in tissue and organs. Rec Res
Soc Finan, Environ Health Sci. 275-80.(2011);
[57]
Barouki R. Can xenobiotics accumulated in adipose tissue contribute to a carcinogenic risk? Ann Endocrinol 74(2): 154-5.(2013);
Related Books
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research-Dementia
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Article Metrics
37
4