The influence of blood lipids on cerebral perfusion by apolipoprotein E status

Elevated blood lipids are strongly associated with increased risk of dementia due to Alzheimer's disease (AD). The apolipoprotein E (APOE) gene plays an important role in lipid transport and is a known genetic risk factor for the development of AD, with increased risk in ε4 carriers. Reduced cerebral blood flow (CBF) is known to precede the onset of AD pathology; however, the associations between blood lipids and cerebral perfusion by APOE status are not completely understood. This study included 65 midlife and older adults (≥50 years old), of which 18 (28%) carried the APOE ε4 allele. Using arterial spin labeling, we measured gray matter and white matter (WM) CBF, and hippocampal blood flow. Pearson correlations and simple linear regressions were used to assess the associations between blood lipids and cerebral perfusion. Serum triglycerides and very-low density lipoprotein cholesterol were negatively associated with GM CBF, WM CBF, and hippocampal blood flow in all participants. However, when stratified by APOE status, the negative associations of triglycerides and very-low density lipoprotein cholesterol on cerebral perfusion were more pronounced in ε4 carriers than non-ε4 carriers, despite no significant group differences in blood lipids. High-density lipoprotein cholesterol was positively associated with only WM CBF, without any differences between APOE status. No other blood lipids were associated with resting cerebral perfusion. These findings suggest that blood lipids can influence resting cerebral perfusion, and ε4 carriers are more negatively affected by this association which may partially explain the increased genetic risk for AD pathology.