Diabetes affects AD through plasma Aβ40: A Mendelian randomization study

Amyloid and tau proteins are important proteins in the pathological changes of Alzheimer’s disease (AD), while Aβ pathology and tau pathology are the most critical factors contributing to the development of AD. Some studies have shown that there is a causal relationship between AD and diabetes mellitus, but there are no studies showing a causal relationship between diabetic traits and AD biomarkers, so further exploration is needed. We first summarized and analyzed the currently published literature on the link between diabetes and AD through a systematic review. Forest plots were used to observe whether there is an association between diabetes and AD. Then a two-sample Mendelian randomization (MR) analysis based on GWAS summary statistics was performed to verify the causal relationship between diabetic traits and AD biomarkers. Based on summary statistics from the GWAS, potential causal relationships between diabetic traits and AD biomarkers were explored separately. The results of the meta-analysis part showed that diabetes can increase the risk of AD. Meanwhile, our two-sample MR results showed a significant causal relationship between diabetes and plasma Aβ40. In addition, our two-sample MR results also showed a causal relationship between increased HbA1c and plasma APLP2. Other diabetic traits may have potential effects on different AD plasma markers.