Wingo TS, et al. - In this case series of plasma samples from 2,125 cases and controls, researchers examined the relationship between circulating cholesterol levels and early-onset Alzheimer disease (EOAD) and identified genetic variants (APOE, APOB, APP, PSEN1, and PSEN2) underlying this possible connection. Data revealed that known AD-causing mutations were seen in around 3% of EOAD cases. According to findings, higher levels of low-density lipoprotein cholesterol (LDL-C) were linked to a greater probability of EOAD, and cases of EOAD were enriched for rare variants of coding in APOB, which codes for LDL-C's major protein. These findings collectively highlight the important role LDL-C plays in the pathogenesis of EOAD and infer a direct link between APOB variants and AD risk.