APP and Alzheimer disease: In addition, AD is a multifactorial neurodegenerative disease, influenced by genetic and environmental risk factors, such as APOE4, sex, and diet, etc. Studies have shown that a high-fat diet (HFD) has significantly increased amyloid plaques in both male and female APP/E4 mice, with RNA sequencing and weighted gene co-expression network analysis showing a positive correlation of the LAPTM5-associated immune response network with the phenotype of female APP/E4-HFD mice [76].