The study investigated the role of comorbidities such as hypertension, stroke and depression in the associations between exposure to fine dust PM2.5 and the development of Alzheimer's disease (AD). It included 27.8 million people aged 65 years and older from the US Medicare program from 2000–2018, where they identified approximately 3 million cases of AD. Exposure to PM2.5 (5-year moving average, interquartile range 3.8 µg/m³) was associated with an increased risk of AD with a hazard ratio of 1.085 (95% CI: 1.078–1.091). This association was stronger in 9.5% of individuals with stroke (HR: 1.096–1.114), while hypertension and depression had little effect modification. PM2.5 increased the risks of hypertension, depression and stroke, which are associated with a higher risk of AD. Mediation by comorbidities was minimal – hypertension mediated 1.6% and stroke 2% of the association. The findings show that the association of PM2.5 with AD is primarily a direct pathway, not through comorbidities.