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

Abstract

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.

Associations of air pollution with all-cause dementia, Alzheimer’s disease, and vascular dementia: a prospective cohort study based on 437,932 participants from the UK biobank

“…Adjusted for age, TDI, sex, smoking, ethnicity, education level, and alcohol use. Martens et al, 2022;Calderon-Garciduenas et al, 2023). However, in our extensive population study, we adopted a novel approach by utilizing 29 independent SNPs significantly associated with AD from previous GWASs to evaluate the genetic risk of AD in the UKB population.…”

History of ALS and the competing theories on pathogenesis: IFCN handbook chapter

“…Missing just a single night’s sleep results in memory, mood, and attentional impairments the next day and disrupted sleep across the lifespan is linked to neurodegeneration ( Krause et al, 2017 , Sabia et al, 2021 ). A variety of sleep disturbances have been described in Alzheimer’s and Parkinson’s diseases ( Calderon-Garciduenas et al, 2023 , Pillai and Leverenz, 2017 , Stefani and Hogl, 2021 ). The sleep abnormalities are typically identified years or even decades prior to the diseases becoming clinically overt, and as such are potentially important early biomarkers of disease.…”

Particulate Matter-Induced Oxidative Stress – Recent Mechanistic Insights from In Vitro Studies

“…Concerning the latter question, the focus has traditionally been on cardiovascular and respiratory effects (Cho et al, 2018). However, growing evidence is indicating links between inhaling PM and conditions such as neurodegenerative disorders (Calderón-Garcidueñas et al, 2023), heightened susceptibility to Sars-cov-2 infection (Marchetti et al, 2023), prenatal and neonatal complications (Janssen et al, 2017), and even fertility issues (Bongaerts et al, 2023) (Figure 2). In the present review we will focus on three main areas: determining the OP of PM (section 2), the oxidative effects and mechanisms triggered by PM (section 3), and the genotoxic and epigenetic effects related to the oxidative stress triggered by PM (sections 4-6).…”