Single-domain magnetic particles with motion behavior under electromagnetic AC and DC fields are a fatal cargo in Metropolitan Mexico City pediatric and young adult early Alzheimer, Parkinson, frontotemporal lobar degeneration and amyotrophic lateral sclerosis and in ALS patients.

Metropolitan Mexico City (MMC) children and young adults exhibit overlapping Alzheimer and Parkinsons' diseases (AD, PD) and TAR DNA-binding protein 43 pathology with magnetic ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs). We studied magnetophoresis, electron microscopy and energy-dispersive X-ray spectrometry in 203 brain samples from 14 children, 27 adults, and 27 ALS cases/controls. Saturation isothermal remanent magnetization (SIRM), capturing magnetically unstable FeNPs ~ 20nm, was higher in caudate, thalamus, hippocampus, putamen, and motor regions with subcortical vs.

Alzheimer and Parkinson diseases, frontotemporal lobar degeneration and amyotrophic lateral sclerosis overlapping neuropathology start in the first two decades of life in pollution exposed urbanites and brain ultrafine particulate matter and industrial nanoparticles, including Fe, Ti, Al, V, Ni, Hg, Co, Cu, Zn, Ag, Pt, Ce, La, Pr and W are key players. Metropolitan Mexico City health crisis is in progress.

The neuropathological hallmarks of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) are present in urban children exposed to fine particulate matter (PM), combustion and friction ultrafine PM (UFPM), and industrial nanoparticles (NPs). Metropolitan Mexico City (MMC) forensic autopsies strongly suggest that anthropogenic UFPM and industrial NPs reach the brain through the nasal/olfactory, lung, gastrointestinal tract, skin, and placental barriers. Diesel-heavy unregulated vehicles are a key UFPM source for 21.

Validation of a Droplet Digital PCR (ddPCR) Assay to Detect Cyanobacterial 16S rDNA in Human Lung Tissue.

Cyanobacteria produce a variety of secondary metabolites, including toxins that may contribute to the development of disease. Previous work was able to detect the presence of a cyanobacterial marker in human nasal and broncoalveolar lavage samples; however, it was not able to determine the quantification of the marker. To further research the relationship between cyanobacteria and human health, we validated a droplet digital polymerase chain reaction (ddPCR) assay to simultaneously detect the cyanobacterial 16S marker and a human housekeeping gene in human lung tissue samples.

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

Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting , are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aβ), 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.

Detection of β-N-methylamino-l-alanine in postmortem olfactory bulbs of Alzheimer's disease patients using UHPLC-MS/MS: An autopsy case-series study.

Introduction: Cyanobacterial blooms produce toxins that may become aerosolized, increasing health risks through inhalation exposures. Health related effects on the lower respiratory tract caused by these toxins are becoming better understood. However, nasal exposures to cyanotoxins remain understudied, especially for those with neurotoxic potential.

Fall Risk, Sleep Behavior, and Sleep-Related Movement Disorders in Young Urbanites Exposed to Air Pollution.

Background: Quadruple aberrant hyperphosphorylated tau, amyloid-β, α-synuclein, and TDP-43 pathology had been documented in 202/203 forensic autopsies in Metropolitan Mexico City ≤40-year-olds with high exposures to ultrafine particulate matter and engineered nanoparticles. Cognition deficits, gait, equilibrium abnormalities, and MRI frontal, temporal, caudate, and cerebellar atrophy are documented in young adults.

Objective: This study aimed to identify an association between falls, probable Rapid Eye Movement Sleep Behavior Disorder (pRBD), restless leg syndrome (RLS), and insomnia in 2,466 Mexican, college-educated volunteers (32.

TDP-43 CSF Concentrations Increase Exponentially with Age in Metropolitan Mexico City Young Urbanites Highly Exposed to PM 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.

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.

miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis.

Background And Objectives: We examined miRNA biomarkers for ALS extracted from extracellular vesicles in blood samples using a large and diverse patient and control population. Different blood collection and storage protocols by different investigators could impact repeatability of miRNA analysis. We tested the hypotheses that miRNA extracted from extracellular vesicles using immunoaffinity purification techniques are robust and repeatable across investigators, laboratories and in a broad ALS population.

A new method for estimating under-recruitment of a patient registry: a case study with the Ohio Registry of Amyotrophic Lateral Sclerosis.

We developed a disease registry to collect all incident amyotrophic lateral sclerosis (ALS) cases diagnosed during 2016-2018 in Ohio. Due to incomplete case ascertainment and limitations of the traditional capture-recapture method, we proposed a new method to estimate the number of cases not recruited by the Registry and their spatial distribution. Specifically, we employed three statistical methods to identify reference counties with normal case-population relationships to build a Poisson regression model for estimating case counts in target counties that potentially have unrecruited cases.

Environmentally Toxic Solid Nanoparticles in Noradrenergic and Dopaminergic Nuclei and Cerebellum of Metropolitan Mexico City Children and Young Adults with Neural Quadruple Misfolded Protein Pathologies and High Exposures to Nano Particulate Matter.

Quadruple aberrant hyperphosphorylated tau, beta-amyloid, α-synuclein and TDP-43 neuropathology and metal solid nanoparticles (NPs) are documented in the brains of children and young adults exposed to Metropolitan Mexico City (MMC) pollution. We investigated environmental NPs reaching noradrenergic and dopaminergic nuclei and the cerebellum and their associated ultrastructural alterations. Here, we identify NPs in the locus coeruleus (LC), substantia nigrae (SN) and cerebellum by transmission electron microscopy (TEM) and energy-dispersive X-ray spectrometry (EDX) in 197 samples from 179 MMC residents, aged 25.

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution.

Exposures to fine particulate matter PM are associated with Alzheimer's, Parkinson's (AD, PD) and TDP-43 pathology in young Metropolitan Mexico City (MMC) residents. High-resolution structural T1-weighted brain MRI and/or Montreal Cognitive Assessment (MoCA) data were examined in 302 volunteers age 32.7 ± 6.

Metals, Nanoparticles, Particulate Matter, and Cognitive Decline.

Exposure to metals is ubiquitous and emission sources include gasoline, diesel, smoke from wildfires, contaminated soil, water and food, medical implants, waste recycling facilities, subway exposures, and occupational environments. PM exposure is associated with impaired cognitive performance, neurobehavioral alterations, incidence of dementia, and Alzheimer's disease (AD) risk. Heavy-duty diesel vehicles are major emitters of metal-rich PM and nanoparticles in Metropolitan Mexico City (MMC).

A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk.

Multiple studies indicate that United States veterans have an increased risk of developing amyotrophic lateral sclerosis (ALS) compared to civilians. However, the responsible etiological factors are unknown. In the general population, specific occupational (e.

Particulate Air Pollution and Risk of Neuropsychiatric Outcomes. What We Breathe, Swallow, and Put on Our Skin Matters.

We appraise newly accumulated evidence of the impact of particle pollution on the brain, the portals of entry, the neural damage mechanisms, and ultimately the neurological and psychiatric outcomes statistically associated with exposures. PM pollution comes from natural and anthropogenic sources such as fossil fuel combustion, engineered nanoparticles (NP ≤ 100 nm), wildfires, and wood burning. We are all constantly exposed during normal daily activities to some level of particle pollution of various sizes-PM (≤2.

Cyanotoxins and the Nervous System.

Cyanobacteria are capable of producing a wide range of bioactive compounds with many considered to be toxins. Although there are a number of toxicological outcomes with respect to cyanobacterial exposure, this review aims to examine those which affect the central nervous system (CNS) or have neurotoxicological properties. Such exposures can be acute or chronic, and we detail issues concerning CNS entry, detection and remediation.

Brainstem Quadruple Aberrant Hyperphosphorylated Tau, Beta-Amyloid, Alpha-Synuclein and TDP-43 Pathology, Stress and Sleep Behavior Disorders.

Quadruple aberrant hyperphosphorylated tau (p-τ), amyloid-β peptide, alpha-synuclein and TDP-43 brainstem and supratentorial pathology are documented in forensic ≤40y autopsies in Metropolitan Mexico City (MMC), and p-τ is the major aberrant protein. Post-traumatic stress disorder (PTSD) is associated with an elevated risk of subsequent dementia, and rapid eye movement sleep behavior disorder (RBD) is documented in PD, AD, Lewy body dementia and ALS. This study aimed to identify an association between PTSD and potential pRBD in Mexico.

Amyotrophic Lateral Sclerosis Risk, Family Income, and Fish Consumption Estimates of Mercury and Omega-3 PUFAs in the United States.

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and lifestyle factors are suspected to play an etiologic role. We previously observed increased risk of ALS associated with high nail mercury levels as an exposure biomarker and thus hypothesized that mercury exposure via fish consumption patterns increases ALS risk. Lifestyle surveys were obtained from ALS patients ( = 165) and = 330 age- and sex-matched controls without ALS enrolled in New Hampshire, Vermont, or Ohio, USA.

The Incidence of Amyotrophic Lateral Sclerosis in Ohio 2016-2018: The Ohio Population-Based ALS Registry.

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal, neuromuscular disease with no cure. ALS incidence rates have not been assessed specifically in Ohio, yet the state contains both metropolitan and rural areas with a variety of environmental factors that could contribute to disease etiology. We report the incidence of ALS in Ohio residents diagnosed from October 2016 through September 2018.

Risk factors for amyotrophic lateral sclerosis: A regional United States case-control study.

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency.

Keratinous biomarker of mercury exposure associated with amyotrophic lateral sclerosis risk in a nationwide U.S. study.

: The majority of cases of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are of unknown etiology. A proportion of these cases are likely to be attributable to contaminant exposures, although the specific environmental etiology of ALS remains largely a mystery. Certain forms of the neurotoxic metal mercury readily cross into the central nervous system.

Gene-Environment-Time Interactions in Neurodegenerative Diseases: Hypotheses and Research Approaches.

Background: Amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's diseases are age-related neurodegenerative diseases. ALS is not a single entity but a syndrome with many different causes. In all 3 diseases, gene mutations account for only 10-15% of cases.

Identifying aerosolized cyanobacteria in the human respiratory tract: A proposed mechanism for cyanotoxin-associated diseases.

Cyanobacteria produce harmful toxins that have been associated with several acute conditions and chronic human diseases, like gastroenteritis, non-alcoholic liver disease, and amyotrophic lateral sclerosis. Aerosol from waterbodies appears to be a likely mechanism for exposure. We conducted a study of human biospecimens focused on the cyanobacterial aerosilization process by evaluating the extent to which cyanobacteria can invade the human respiratory tract.

Toenail mercury Levels are associated with amyotrophic lateral sclerosis risk.

Introduction: Mercury is a neurotoxic metal that is potentially a risk factor for amyotrophic lateral sclerosis (ALS). Consumption of methylmercury contaminated fish is the primary source of US population exposure to mercury.

Methods: We used inductively coupled plasma mass spectrometry to measure levels of mercury in toenail samples from patients with ALS (n = 46) and from controls (n = 66) as a biomarker of mercury exposure.

Medical history of chemotherapy or immunosuppressive drug treatment and risk of amyotrophic lateral sclerosis (ALS).

A recent population-based analysis demonstrated lower risk of the lethal degenerative neuromuscular disease, amyotrophic lateral sclerosis (ALS) associated with history of the use of 'antineoplastic agents' and 'immunosuppressants'. To see if this finding was generalizable to other ALS cohorts, we examined associations between use of these agents and ALS risk in an independent case-control study of n = 414 ALS patients and n = 361 controls in an Eastern US population. Controls were sampled from the general population and among non-neurodegenerative disease patients.