Air Pollution and Alzheimer Disease Pathology: What’s the Link?

Traffic-related pollution is associated with an increased prevalence of neuritic plaques on autopsy among patients with Alzheimer disease (AD), particularly for individuals without apolipoprotein E (APOE) ε4 alleles, according to study findings published in Neurology. 

Studies have shown that exposure to traffic-related air pollution, specifically fine particulate matter less than 2.5 μm in diameter (PM_2.5), is associated with dementia and other measures of cognitive decline. The APOE gene is a major risk factor for AD and has been hypothesized to modify the association between PM_2.5 and AD. Researchers conducted a cross-sectional study to address the gap in data regarding the impact of PM_2.5 on AD and the APOE genotype. 

The Emory Goizueta Alzheimer’s Disease Research Center (ADRC) has a brain bank for AD research. Most of the brain tissue donors were research participants who were evaluated yearly. In 2020, there were 1011 total donors, and 224 were included in the final analysis. Participants had residential addresses within Georgia, were age 55 and older at death, and were deceased after 1999. 

The neuropathology of AD was evaluated using the Braak stage, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) score, and combined AD neuropathologic change (ABC) score. A high Braak stage score is associated with wider distribution of neurofibrillary tangles in the brain. The CERAD score shows the prevalence of neuritic plaques, with higher levels indicating frequent plaques. The ABC score combines the Braak and CERAD scores with the distribution of amyloid plaques in the brain, with 4 levels indicating changes in neuropathology (none, low, intermediate, or high).

Of the 224 participants, 203 were White (90.6%), 133 were men (59.4%), and 169 had earned at least a college degree (75.5%). The average age at death for participants was 76. Among this cohort, 97 (43.3%) participants had 1 APOE ε4 copy and 30 (13.4%) had 2 copies. A total of 102 (45.5%) participants had the highest Braak stage, 158 (70.5%) had the highest CERAD score category, and 130 (58%) had the highest ABC score category. 

Using the ABC score, 72.7% of participants had pathology-confirmed AD, which was classified as intermediate or high ABC grading. The study results show that PM_2.5 was significantly associated with CERAD score in a 1-year exposure window (odds ratio [OR], 1.92; 95% CI, 1.12-3.30) and a 3-year exposure window (OR, 1.87; 95% CI, 1.01-3.17).

There was a harmful association observed between PM_2.5 and Braak stage and ABC scores, although the association was not statistically significant. The strongest association between PM_2.5 and all neuropathology outcomes were for those without the APOE ε4 variant, but these findings were not statistically significant. 

Study limitations included that the ADRC cohort was not a population-based sample, had a relatively small sample size, included a majority White and highly educated population, and only considered the address available at death. 

“More research is needed to establish causality for the association between PM_2.5 and AD, including epidemiologic and mechanistic studies. Future studies should also investigate the association between PM_2.5 and other dementia-related pathologies, including cerebrovascular pathology,” the study authors concluded.