AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 48:63–77 (2005) Potential Occupational Risks for Neurodegenerative Diseases Robert M Park, MS , 1 A Paul A Schulte, PhD , 1 Joseph D Bowman, PhD , CIH , 2 James T Walker, PhD , 3 Stephen C Bondy, MA , PhD , 4 Michael G Yost, MS , PhD , 5 Jennifer A Touchstone, MS , 5 and Mustafa Dosemeci, PhD6 Background Associations between occupations and neurodegenerative diseases (NDD) may be discernable in death certificate data Methods Hypotheses generated from 1982 to 1991 study were tested in data from 22 states for the years 1992–1998 Specific occupations and exposures to pesticides, solvents, oxidative stressors, magnetic fields, and welding fumes were evaluated Results About one third (26/87) of the occupations hypothesized with neurodegenerative associations had statistically significant elevated mortality odds ratios (MOR) for the same outcome Occupations with the largest MORs were (a) for presenile dementia (PSD)— dentists, graders/sorters (non-agricultural), and clergy; (b) for Alzheimer’s disease (AD)—bank tellers, clergy, aircraft mechanics, and hairdressers; (c) for Parkinson’s disease (PD)—biological scientists, clergy, religious workers, and post-secondary teachers; and (d) for motor neuron disease (MND)—veterinarians, hairdressers, and graders and sorters (non-agricultural) Teachers had significantly elevated MORs for all four diseases, and hairdressers for three of the four Non-horticultural farmers below age 65 had elevated PD (MOR ¼ 223, 95% CI ¼ 147–326), PSD (MOR ¼ 222, 95% CI ¼ 110–405), and AD (MOR ¼ 176, 95% CI ¼ 104–281) Sixty hertz magnetic fields exhibited significant exposure-response for AD and, below age 65, for PD (MOR ¼ 187, 95% CI ¼ 114–298) and MND (MOR ¼ 163, 95% CI ¼ 110–239) Welding had elevated PD mortality below age 65 (MOR ¼ 177, 95% CI ¼ 108–275) Conclusions Support was observed for hypothesized excess neurodegenerative disease associated with a variety of occupations, 60 Hz magnetic fields and welding Am J Ind Med 48:63–77, 2005 Published 2005 Wiley-Liss, Inc { KEY WORDS: Alzheimer’s disease; hairdresser; motor neuron disease; magnetic field; Parkinson’s disease; pesticide; welding Abbreviations: AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; BOC, Bureau of the Census; EMF, electromagnetic field; MND, motor neuron disease; MOR, mortality odds ratio; NDD, neurodegenerative disease; PD, Parkinson’s disease; PMR, proportionate mortal- ity ratios; PSD, presenile dementia Education and Information Division, National Institute for Occupational Safety and Health, Cincinnati, Ohio Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Cincinnati, Ohio Division of Surveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, Cincinnati, Ohio Department of Community & Environmental Medicine, University of California, Irvine, California Published 2005 Wiley-Liss, Inc This article is a US Government work and, as such, is in the public domain in the United States of America Department of Environmental Health, University of Washington, Seattle,Washington Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland *Correspondence to: Robert M Park, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Education and Information Division, MS C-15, 4676 Columbia Parkway, Cincinnati, OH 45226 E-mail: rhp9@cdcgov Accepted 27 March 2005 DOI 101002/ajim20178 Published online in Wiley InterScience (wwwintersciencewileycom)

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Potential Occupational Risks for Neurodegenerative Diseases

OBJECTIVES: To identify potential occupational risk factors, this study examined the occupational occurrence of various neurodegenerative diseases. METHODS: Death certificates from 27 states in the National Occupational Mortality Surveillance System were evaluated for 1982 to 1991. Proportionate mortality ratios were calculated by occupation for presenile dementia, Alzheimer's disease, Parkinson's disease, and motor neuron disease. RESULTS: Excess mortality was observed for all four categories in the following occupational categories: teachers; medical personnel; machinists and machine operators; scientists; writers/designers/entertainers; and support and clerical workers. Clusters of three neurodegenerative diseases were also found in occupations involving pesticides, solvents, and electromagnetic fields and in legal, library, social, and religious work. Early death from motor neuron disease was found for firefighters, janitors, military personnel, teachers, excavation machine operators, and veterinarian...

Neurodegenerative diseases: occupational occurrence and potential risk factors, 1982 through 1991.

Degeneration of neuronal cells due to oxidative stress--microglial contribution.

This review will summarize current understanding of the molecular and cellular mechanisms of excitotoxicity, the organization of glutamate systems in relation to ALS and evidence that excitotoxicity is relevant to the pathogenesis of ALS. NEUROLOGY 1996;47(Suppl 4): S221-S227

Excitotoxicity in ALS.

Transgenic (NFHLacZ) mice expressing a fusion protein composed of a truncated high-molecular-weight mouse neurofilament (NF) protein (NFH) fused to beta-galactosidase (LacZ) develop inclusions in neurons throughout the CNS. These inclusions persist from birth to advanced age and contain massive filamentous aggregates including all three endogenous NF proteins and the NFHLacZ fusion protein. Further, the levels of endogenous NF proteins are selectively reduced in NFHLacZ mice. Because these inclusions resemble NF-rich Lewy bodies (LBs) in Parkinson's disease and LB dementia, we asked whether these lesions compromised the viability of affected neurons during aging. We studied hippocampal CA1 neurons, nearly all of which harbored inclusions (type I) devoid of cellular organelles, and cerebellar Purkinje cells, nearly all of which accumulated inclusions (type II) containing numerous entrapped organelles. Purkinje cells with type II inclusions began to degenerate in the NFHLacZ mice at approximately 1 year of age, and most were eliminated by 18 months of age. In contrast, there was no significant loss of type I inclusion-bearing CA1 neurons with age. These data suggest that the sequestration of cellular organelles in type II inclusions may isolate and impair the function of these organelles, thereby rendering Purkinje cells selectively vulnerable to degeneration with age as in neurodegenerative diseases of the elderly characterized by accumulation of LBs.

https://www.jneurosci.org/content/jneuro/17/3/1064.full.pdf

Selective degeneration fo Purkinje cells with Lewy body-like inclusions in aged NFHLACZ transgenic mice.

Conventional definitions of neurodegeneration imply that it is a process of idiopathic progressive neuronal death, generally occurring in a selective distribution that often involves hnctionally related pathways. Such a definitibn would encompass the orchestrated death of neurons that takes place in fetal development, and the regionally heterogeneous attrition that occurs in the aging nervous system. However, fetal development and aging are normal occurrences, and the term neurodegeneration implies abnormality. Thus neurodegeneration implicitly denotes disease, and there can be no doubt that the three major examples of this are dementia of Alzheimer's type (DAT), idiopathic parkinsonism (IP), and amyotrophic lateral sclerosis (ALS). A shared pathologic feature of these disorders is the accumulation of cytoskeletal products, which seems to represent a nonspecific marker of cell stress, rather than providing a clue to a specific pathogenesis. For example, the Lewy body has been reported in such a wide range of disturbances that it is difficult to argue that its presence sheds any light on etiology. The crucial question is: What causes neuronal stress and, ultimately, neuronal death?

B. J. Snow

Papers

Theories of Neurodegeneration