Airborne lead and polychlorinated biphenyls (PCBs) are associated with amyotrophic lateral sclerosis (ALS) risk in the U.S

Andrew, Angeline S.; Zhou, Jie; Gui, Jiang; Harrison, Antoinette; Shi, Xun; Li, Meifang; Guetti, Bart; Nathan, Ramaa; Tischbein, Maeve; Pioro, Erik P.; Stommel, Elijah W.; Bradley, Walter G.

doi:10.1016/j.scitotenv.2022.153096

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…Tactical operations officers consisted primarily of pilots, aircraft crew, missile, and combat operations staff. These data suggest that environmental concerns should be explored among those who routinely work with jet aircraft and develop ALS at a young age ( Hayes et al, 2021 ; Andrew et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…The etiology of sporadic ALS (sALS) is often attributed with little evidence to undefined environmental agents acting on a genetic susceptibility to the disease ( Al-Chalabi et al, 2010 ; Vasta et al, 2021 ; Goutman et al, 2022 ). Viruses, fungi, cyanobacteria, heavy metals, pesticides, persistent toxicants, solvents, electromagnetic radiation, electric shock, cigarette smoke, DNA damage, impaired DNA repair, epigenetic changes, immune dysfunction, endocrine abnormalities, excessive exercise, professional soccer, and trauma, have all been associated with sALS ( Tandan and Bradley, 1985 ; Chiò et al, 2005 ; Armon, 2009 ; Pritchard and Silk, 2014 ; Alonso et al, 2015 ; Coppedè and Migliore, 2015 ; Harwood et al, 2016 ; Schwartz and Klug, 2016 ; Riancho et al, 2018 ; French et al, 2019a ; Filippini et al, 2020 ; Andrew et al, 2022 ; Re et al, 2022 ), but convincing evidence of a causative role for any of these factors has yet to be demonstrated. Among heavy metals, lead has been proposed as a risk factor for ALS ( Kamel et al, 2002 ; Fang et al, 2010 ; Meng et al, 2020 ; Andrew et al, 2022 ) but the association is considered weak ( Wang et al, 2014 ; Newell et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Viruses, fungi, cyanobacteria, heavy metals, pesticides, persistent toxicants, solvents, electromagnetic radiation, electric shock, cigarette smoke, DNA damage, impaired DNA repair, epigenetic changes, immune dysfunction, endocrine abnormalities, excessive exercise, professional soccer, and trauma, have all been associated with sALS ( Tandan and Bradley, 1985 ; Chiò et al, 2005 ; Armon, 2009 ; Pritchard and Silk, 2014 ; Alonso et al, 2015 ; Coppedè and Migliore, 2015 ; Harwood et al, 2016 ; Schwartz and Klug, 2016 ; Riancho et al, 2018 ; French et al, 2019a ; Filippini et al, 2020 ; Andrew et al, 2022 ; Re et al, 2022 ), but convincing evidence of a causative role for any of these factors has yet to be demonstrated. Among heavy metals, lead has been proposed as a risk factor for ALS ( Kamel et al, 2002 ; Fang et al, 2010 ; Meng et al, 2020 ; Andrew et al, 2022 ) but the association is considered weak ( Wang et al, 2014 ; Newell et al, 2021 ). One group has proposed sALS arises from an opportunistic fungal infection ( French et al, 2019a , b ), and another has published evidence of mixed fungal and bacterial infection in the CNS of a small number of sALS cases ( Alonso et al, 2017 , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research

et al. 2023

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The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research

et al. 2023

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“…Strikingly, MMC residents have cellular, subcellular and immunoreactive pathology in precisely the same regions [ 2 , 46 , 69 ]. Moreover, Andrew and colleagues [ 78 ] identified contaminants found to have a strong association with ALS risk in the US, including airborne lead (false discovery rate (FDR) = 0.00077), primarily produced by small aircraft, and polychlorinated biphenyls (PCBs), such as heptachlorobiphenyl (FDR = 3.60E-05) emitted by power plants burning biomass and industrial boilers. This analysis supports neurotoxic airborne metals and PCBs as risk factors for ALS.…”

Section: Discussionmentioning

confidence: 99%

TDP-43 CSF Concentrations Increase Exponentially with Age in Metropolitan Mexico City Young Urbanites Highly Exposed to PM2.5 and Ultrafine Particles and Historically Showing Alzheimer and Parkinson’s Hallmarks. Brain TDP-43 Pathology in MMC Residents Is Associated with High Cisternal CSF TDP-43 Concentrations

Calderón‐Garcidueñas

Stommel

Lachmann³

et al. 2022

Toxics

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Environmental exposures to fine particulate matter (PM2.5) and ultrafine particle matter (UFPM) are associated with overlapping Alzheimer’s, Parkinson’s and TAR DNA-binding protein 43 (TDP-43) hallmark protein pathologies in young Metropolitan Mexico City (MMC) urbanites. We measured CSF concentrations of TDP-43 in 194 urban residents, including 92 MMC children aged 10.2 ± 4.7 y exposed to PM2.5 levels above the USEPA annual standard and to high UFPM and 26 low pollution controls (11.5 ± 4.4 y); 43 MMC adults (42.3 ± 15.9 y) and 14 low pollution adult controls (33.1 ± 12.0 y); and 19 amyotrophic lateral sclerosis (ALS) patients (52.4 ± 14.1 y). TDP-43 neuropathology and cisternal CSF data from 20 subjects—15 MMC (41.1 ± 18.9 y) and 5 low pollution controls (46 ± 16.01 y)—were included. CSF TDP-43 exponentially increased with age (p < 0.0001) and it was higher for MMC residents. TDP-43 cisternal CSF levels of 572 ± 208 pg/mL in 6/15 MMC autopsy cases forecasted TDP-43 in the olfactory bulb, medulla and pons, reticular formation and motor nuclei neurons. A 16 y old with TDP-43 cisternal levels of 1030 pg/mL exhibited TDP-43 pathology and all 15 MMC autopsy cases exhibited AD and PD hallmarks. Overlapping TDP-43, AD and PD pathologies start in childhood in urbanites with high exposures to PM2.5 and UFPM. Early, sustained exposures to PM air pollution represent a high risk for developing brains and MMC UFPM emissions sources ought to be clearly identified, regulated, monitored and controlled. Prevention of deadly neurologic diseases associated with air pollution ought to be a public health priority and preventive medicine is key.

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“…Chronic exposures to outdoor concentrations of PM 2.5 above WHO air quality guidelines (annual 5 µg/m 3 ) caused 6.4 million premature deaths and 93 billion days lived with illness in residents worldwide in 2019 (1). Exposures to traffic-generated pollutants, residency close to high-traffic roads, incomplete combustion emissions, firepit emissions, and in vitro experimental PM exposures of neural tissues, among other sources, have all been associated with extensive neural damage and increases in neurodegenerative diseases, including AD, PD, and ALS for the last two decades (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Millions of US residents are exposed to wild forest fires and live near high-volume traffic roads and traffic-related air pollution (TRAP) (18,19).…”

Section: Introductionmentioning

confidence: 99%

Sleep matters: Neurodegeneration spectrum heterogeneity, combustion and friction ultrafine particles, industrial nanoparticle pollution, and sleep disorders—Denial is not an option

Calderón‐Garcidueñas

Torres‐Jardón²,

Greenough³

et al. 2023

Front. Neurol.

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Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aβ1 − 42), α-synuclein (α syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority.

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Airborne lead and polychlorinated biphenyls (PCBs) are associated with amyotrophic lateral sclerosis (ALS) risk in the U.S

Cited by 9 publications

References 46 publications

Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research

Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research

Sleep matters: Neurodegeneration spectrum heterogeneity, combustion and friction ultrafine particles, industrial nanoparticle pollution, and sleep disorders—Denial is not an option

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