Air pollution exposure promotes Alzheimer’s disease-related hallmarks in the brains of children.

Components present in air pollution – a mixture of chemicals, gases, and particulate matter – can cross biological barriers, including the blood-brain barrier. Evidence suggests that children exposed to air pollution exhibit altered brain structure and metabolic function and demonstrate impaired cognitive performance. A 2018 study identified pathological hallmarks associated with Alzheimer’s disease in the brains of children and young adults living in Mexico City, an area known for its high levels of air pollution.

The primary pathological hallmarks associated with Alzheimer’s disease are amyloid-beta plaques and tau neurofibrillary tangles. Amyloid-beta is a toxic 42-amino acid peptide that clumps together, forming plaques in the brain. Tau is a protein that, when modified via the chemical process of phosphorylation, can form aggregates called neurofibrillary tangles in the brain. Scientists classify the severity of neurofibrillary tangle formation according to the Braak staging system, which ranks severity on a scale of I to VI, with VI being the most severe.

The investigators examined autopsy-derived brain tissues from 203 subjects living in Mexico City, ranging in age from 11 months to 40 years, to identify the presence of amyloid-beta plaques and tau neurofibrillary tangles. They calculated the subjects' cumulative burden of particulate matter exposure based on their place of residence and noted the subjects' cause of death. They also conducted genotyping to determine whether the subjects were carriers of APOE4, a genetic variant that increases a person’s risk of developing Alzheimer’s disease.

They found that 99.5 percent of the subjects' brains exhibited abnormally high levels of amyloid-beta and hyperphosphorylated tau, even as early as 11 months of age. Approximately one-fourth of subjects between the ages of 30 and 40 years exhibited stage III or IV neurofibrillary tangles. Subjects who carried the APOE4 variant were at least 23 times more likely to exhibit stage IV tangles. Interestingly, APOE4 carriers were nearly five times more likely to commit suicide than non-carriers.

These findings suggest that exposure to air pollution in early life increases a person’s risk for developing Alzheimer’s disease. People who carry the high-risk genetic variant APOE4 are at substantially greater risk and may, additionally, be vulnerable to greater suicide risk. Omega-3 fatty acids help maintain blood-brain barrier integrity and may reduce the risk of Alzheimer’s disease in APOE4 carriers. Learn more in this open-access peer-reviewed article by Dr. Rhonda Patrick.

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