A total of 549 participants (298 AD patients, 251 HCs) were included in the study. The mean (SD) age of AD patients was 76.07 (7.12) years old, and the HCs were 65.85 (11.33) years old, so the age factor was adjusted in the subsequent lipid analysis. There were 113 male people in AD and 103 male people in HCs. In AD patients, the mean (SD) course of the disease was 2.5 (2.52) years, the mean (SD) of MMSE score was 18 (5.21), the mean (SD) of MOCA was 12.48 (3.56) (Table 1).
Table 1
APOE gene and sex distribution in AD group and HCs group (mean±standard deviation)
| | AD (n=298) | HCs (n=251) | t/χ2 | p-value |
Age and examination, yr | | 76.07±7.12 | 65.85±11.33 | 12.38 | <0.001 |
Course of the disease, yr | | 2.54±2.52 | | | |
MoCA | | 12.48±5.21 | 24.00±1.48 | 21.428 | <0.001 |
MMSE | | 18±3.56 | | | |
APOEε4 | APOE4 +, n (%) | 149(50.00%) | 38(20.30%) | 73.719 | <0.001 |
APOEε2 | APOE2 +, n (%) | 18(6.00%) | 53(21.10%) | 27.498 | <0.001 |
sex | Male, n (%) | 113(37.90%) | 103(41.00%) | 0.554 | 0.457 |
subtypes | | | | 79.39 | <0.001 |
| e2/e2, e2/e3, e3/e3, n (%) | 149(41.20%) | 213(58.80%) | 73.719 | <0.001 |
| e2/e4, e3/e4, n (%) | 131(44.00%) | 35(13.90%) | 58.19 | <0.001 |
| e4/e4, n (%) | 18(6.00%) | 3(1.20%) | 8.694 | 0.003 |
APOE haplotypes | | | | 99.458 | <0.001 |
| e2/e2, n (%) | 0 | 5(0.90%) | 5.991 | 0.02 |
| e2/e3, n (%) | 18(6.00%) | 41(16.30%) | 15.053 | <0.001 |
| e3/e3, n (%) | 131(44.00%) | 167(66.50%) | 27.977 | <0.001 |
| e2/e4, n (%) | 0 | 7(2.80%) | 8.461 | 0.004 |
| e3/e4, n (%) | 131(44.00%) | 28(11.20%) | 71.263 | <0.001 |
| e4/e4, n (%) | 18(6.00%) | 3(1.20%) | 8.694 | 0.003 |
APOE Gene analysis in AD patients and HCs
There were significant differences in the haplotype frequency of APOEε4 and APOEε2 between the AD and HCs (Table 1). A significantly higher proportion of APOEε4 carriers and a lower proportion of APOEε2 carriers were found in the AD group than those in the HCs (Table 1).
Comparison of lipid profiles between AD patients and HCs
The levels of TC and LDL in the AD group were higher than those in the HCs group. In the subgroup analysis based on APOE alleles, AD patients carrying APOEε4 had higher levels of TC and LDL than HCs with APOEε4 allele; AD patients without APOEε2 allele had increased TC and LDL levels than HCs without APOEε2 allele. In subgroup analysis based on sex, TC and LDL levels in the AD group were significantly higher than in the HCs group in both sexes. A subgroup analysis combined sex and APOE haplotypes showed that increased levels of TC and LDL in female APOEε4 carriers than female non-APOEε4 carriers and in male non-APOEε2 carriers than male APOEε2 carriers (Figure 1). In addition, serum HDL level in the AD group was higher than those in the HCs group. Subgroup analysis showed that the change of HDL level was found in AD patients with APOEε4 allele and without APOEε2 allele, as well as in male non-APOEε2 carriers and male APOEε4 carriers (Figure 1).
Comparison of lipid profiles between APOEε4 allele-carriers and non-APOEε4 allele-carriers
The levels of TC and LDL in the APOEε4 carriers were higher than those in non-APOEε4 carriers. In the subgroup analysis based on disease, we found that AD patients with APOEε4 had significantly higher levels of TC and LDL than AD patients without APOEε4. No differences in the levels of TC and LDL between HCs with and without APOEε4. Furthermore, In the subgroup analysis based on sex, significantly higher levels of TC and LDL were only found in female AD patients with APOEε4 than without APOEε4 female AD patients. However, no differences were found between male AD patients with and without APOEε4 (Figure 2).
Comparison of lipid profiles between APOEε2 allele-carriers and non-APOEε2 allele-carriers
The levels of TC and LDL in the APOEε2 carriers were lower than those in non-APOEε2 carriers. In the subgroup analysis based on sex and disease, similar changes in LDL levels were found in almost all subgroups except the female control population. The TC levels were lower in AD patients with the APOEε2 allele than in AD patients without the APOEε2 allele, but no such change was observed in the HCs. In addition, the TC of APOEε2 carriers was lower than that of non-carriers in the male AD population, but there was no such change in the female AD population, female HCs, and male HCs (Figure 3).
Comparison of lipid profiles between the male and the female
The TC, HDL, and LDL levels in the female population were higher than the male population. In order to exclude the effect of disease and APOE gene, subgroup analyses were performed, and the results showed that sex had similar effects on TC and LDL in AD patients, APOEε4 carriers, and APOEε2 non-carriers. In the control participants and APOEε4 non-carriers, TC and HDL in the female population were higher than the male population (Figure 4).
Complex interactions exist between AD, APOE haplotypes, lipid profiles and sex
Age, gender, course of the AD disease, APOEε4, and blood lipids level were considered influencing factors for Logistics regression analysis, and we found that age and APOE4 were important risk factors, while the blood lipids were not significantly related with AD. When TG, TC, HDL, and LDL were taken as targets to study the relationship with AD, no correlation was found between lipid profiles and AD through logistics regression analysis. However, in the subgroup analysis, adjusted APOE and sex, we found that LDL increased the risk of AD in females with the APOEε4 allele, that is, for every 1 unit increase in LDL, the risk of AD increased 898.46 times in the female population with APOEε4 (P = 0.04). Therefore the increased LDL level may increase the risk of AD in female people carrying APOEε4.