Alzheimer neuropathological change, α-synuclein and transactive response DNA-binding protein of 43 kDa expression in children and young adult brains from forensic autopsies: Value for early measurement of abnormal protein expression prevalence in neurodegenerative diseases

Alzheimer disease (AD) neuropathologic change (ADNPC), Parkinson disease (PD) α-synuclein (α-Syn), and TAR DNA-binding protein 43 (TDP-43) pathology overlap in a continuum in fine particulate matter (PM2.5)-exposed Metropolitan Mexico City (MMC) children and young adult forensic autopsy brains. This report focuses on a forensic targeted immunohistochemistry protocol to assess ADNPC, α-Syn and TDP-43 in ≤40y subjects, and to define their relationship with cumulative PM2.5 (CPM) exposures. We proposed an early measurement of abnormal protein expression to evaluate neurodegenerative disease prevalence in exposed PM2.5 urban young populations. We studied 189 autopsies average age 26±10y, including 179 MMC ≤40y olds and 10 low pollution controls. Among MMC adults 18-40y, 11.3% exhibited ADNPC alone; 50% had ADNPC + PD, 32.0% had ADNPC + PD + TDP-43 and 6.7% had ADNPC + TDP-43 pathology. In 37 children (13.0±4.8y), 24.3% had ADNPC, 37.8% had ADNPC + PD, 32.4% had ADNPC + PD + TDP-43; 5.4% had ADNPC + TDP-43 pathology. The overlapping children's neuropathology was documented under low CPM. We suggest that measurements of abnormal protein expression to evaluate neurodegenerative disease in young PM2.5-exposed young urban populations in US autopsies will define the prevalence and overlap of early neurodegenerative biological markers. This information guide preventive medicine, health services, environmental PM2.5 emission control and early neuroprotection from potentially preventable air pollution-associated neurodegenerative diseases.