Background: We investigated the associations of genetic risk score for Alzheimer's disease (GRS-AD) with cardiometabolic risk from early childhood over a 20-year follow-up.

Methods: The STRIP study included 1062 children at baseline. GRS-AD was calculated for 631 participants using 22 independent genetic risk variants, including APOE ε2 and ε4 alleles, and excluding them (non-APOE-GRS-AD). We repeatedly measured waist circumference, high-density (HDL-C) and low-density (LDL-C) lipoprotein cholesterol, triglycerides, glucose, insulin, and blood pressure. The data were analysed with generalised additive mixed models.

Results: GRS-AD was directly associated with serum LDL-C (unstandardised β = 0.140, 95% CI = 0.084 to 0.195) and inversely with HDL-C (β = -0.026, 95% CI = -0.044 to -0.009). GRS-AD was inversely associated with serum HDL-C in males (β = -0.044, 95% CI = -0.070 to -0.018) but not in females (β = -0.010, 95% CI = -0.032 to 0.012). The associations were diluted when the non-APOE-GRS-AD was applied.

Conclusion: A genetic predisposition to AD may alter lipid metabolism from early childhood.

Impact: While Alzheimer's disease and cardiometabolic diseases may have shared genetic determinants, the associations between genetic susceptibility for Alzheimer's disease and increased cardiometabolic risk from childhood to young adulthood are poorly understood. We investigated the associations of genetic risk score for Alzheimer's disease with cardiometabolic risk from early childhood over a 20-year follow-up. We found that a higher genetic risk score for Alzheimer's disease was associated with higher LDL cholesterol, non-HDL cholesterol, and ApoB, and with lower serum HDL cholesterol and ApoA1. These findings suggest that a genetic predisposition to Alzheimer's disease may alter lipid metabolism from early childhood.