Apolipoprotein B (APOB) is a critical lipoprotein implicated in the synthesis and transport of low-density lipoprotein (LDL) cholesterol, which is known to be deleterious to human health. An increasing body of research, encompassing both clinical and animal model studies, has highlighted a significant role for APOB in the pathogenesis of Alzheimer's disease (AD). Nevertheless, the direct causal relationship between APOB and AD remains elusive. Utilizing publicly available genome-wide association study (GWAS) data, we employed Mendelian randomization to uncover evidence suggesting that APOB elevates the risk of developing AD (OR=1.551, 95% CI=1.091-2.202, P=0.014). Conversely, we did not identify an inverse causal relationship between them (OR=1.021, 95% CI=0.957-1.089, P=0.529). Further analysis of apolipoprotein A1 (APOA1) revealed no beneficial impact on AD, nor a direct causal effect of AD on APOA1 levels (P=0.808, 0.259). In summary, our study establishes a direct causal effect of APOB on the development of AD, offering novel genetic evidence that APOB enhances the risk of AD. This finding contributes to a deeper understanding of the intricate pathogenesis of AD

Guofu Zhang is the director of the Department of Geriatric Psychiatry of The Affiliated Mental Health Center of Jiangnan University. He holds the title of chief physician and is also a master's supervisor. He is a standing member of the Psychiatry Branch of the Chinese Association of Research Hospitals, a member of the Psychiatric Rehabilitation Working Committee of the Psychiatrist Branch of the Chinese Physicians Association, a member of the Psychiatry Committee of the Jiangsu Provincial Medical Association, and the vice president and secretary general of the Wuxi Psychological Association