Abstract
BACKGROUND: Evidence suggests that lipoprotein metabolism play a crucial role in Alzheimer's disease (AD). However, their involvement in late-onset AD (LOAD) remains unclear. OBJECTIVE: This study aimed to uncover potential associations between lipoprotein metabolism and clinical LOAD diagnosis, cognitive function, and treatment. METHODS: We performed a lipidomic analysis of plasma samples from 46 individuals with LOAD and 16 healthy controls to investigate the potential association between lipoprotein profiles, LOAD diagnosis and cognitive function. Then, we conducted a protein-protein interaction analysis to explore the potential therapeutic role of lipoprotein molecules in LOAD. RESULTS: Our findings revealed that ApoA2 and HDL ApoA2 may be negatively associated with LOAD risk (odds ratio [OR] = 0.798, 95% confidence interval [CI] = 0.654-0.973, p = 0.026; OR = 0.785, 95% CI = 0.634-0.972, p = 0.026, respectively), while LDL-3 triglycerides showed a potential positive association (OR = 6.051, 95% CI = 1.789-20.470, p = 0.004). Additionally, HDL-4 ApoA1 may be positively correlated with cognitive function in LOAD (p = 0.047, r² = 0.087). Moreover, our findings suggest that ApoA2 may interact with targets of approved AD drugs. CONCLUSIONS: This study identifies potential key lipoprotein alterations associated with LOAD diagnosis and cognitive function, emphasizing the role of lipidomic insights in understanding and treating LOAD.