Cortical, subcortical, and cerebellar atrophy and cognition deficits in Metropolitan Mexico City teens and young adults exposed to fine particulate matter (PM2.5) - neurodegeneration is in progress

Exposure to environmental fine particulate matter (PM 2.5 ), ultrafine PM (UFPM) and nanoparticles (NPs) are associated with accumulation of amyloid-β 1–42 peptides, phosphorylated-Tau, alpha-synuclein and transactive response DNA binding-protein-43 misfolded aberrant proteins, consistent with the biological definitions of overlapping Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) in 99% of ≤40-year-old Metropolitan Mexico City (MMC) forensic autopsies. Structural and volumetric brain responses in vivo are critical in young MMC residents. We performed volumetric and whole-brain correlation analyses in 75 healthy volunteers: 45 MMC 31.2 ± 14.7 y old and 30 low-pollution 31.8 ± 4.8 y old controls, matched by ethnicity, socioeconomic status, nutrition, and BMI. MMC residents exhibited fronto-parietal and temporal lobes, precentral gyrus, hippocampi, basal ganglia, thalamus, amygdala and cerebellar atrophy. The most common atrophy pattern was cortical first parietal and fronto-parietal lobes, combined with gray matter (GM) atrophy in cerebellar lobules IV and V left and right III, IV and V and VI.MMC participants had mild cognitive impairment (Montreal Cognitive Assessment Score 22.8 ± 3.2). GM atrophy involving right globus pallidus and pulvinar and cerebellar white matter (WM) bilaterally were associated with lower cognitive performance and high BMI to subiculum, posterior orbital gyrus and insula, inferior temporal gyrus, supplementary motor cortex, and cuneus WM atrophy. PM 2.5 exposure and BMI appear to play key roles in early neurodegenerative disease biology and may contribute to adverse effects on academic and occupational performance, neuropsychiatric disorders, behavioral regulation, risk of substance use initiation, and psychopathy. Neuroradiologists across the world need to know cortical and subcortical, including extensive hippocampal, stratium and cerebellar atrophy identifies overlapping patterns of regional atrophy associated with MCI, AD, bvFTD, PD and ALS, in young urbanites. There is an urgent need for early pediatric neuroprevention interventions, non-invasive AD, PD and TDP-43 biomarkers, in-depth characterization of emission pollutants exposures and their effective control. Denial is no longer an option.