Modulatory effect of blood LDL cholesterol on the association between cerebral Aβ and tau deposition in older adults

Background: We aimed to examine whether higher blood low-density lipoprotein cholesterol (LDL-C) synergistically moderates the association of cerebral beta-amyloid (Aβ) with tau deposition in older adults with diverse cognitive spectrum. The associations of various blood lipids, including total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) with cerebral Aβ and tau, and white matter hyperintensities (WMHs) were also explored. Methods: A comprehensive clinical evaluation, serum lipid measurements, [11C] Pittsburgh Compound B-positron emission tomography (PET), [18F] AV-1451 PET, and magnetic resonance imaging were performed on all participants. Results: A total of 136 older adults with normal cognition, mild cognitive impairment or Alzheimer’s disease (AD) dementia were included. There was a significant Aβ x LDL-C interaction effect on tau deposition indicating a synergistic moderation effect of LDL-C on the relationship between Aβ and tau deposition. Subsequent subgroup analysis showed that the positive association between Aβ and tau deposition was stronger in higher LDL-C group than in lower LDL-C group. In contrast, other lipids (i.e., TC, HDL-C and TG) did not show a similar moderation effect on the relationship between Aβ deposition and tau deposition. Exploratory analysis showed a positive relationship between serum LDL-C and WMH volume, while there were no significant association between any lipids and AD pathologies. Conclusion: Our findings suggest that blood LDL-C synergistically increases tau pathology with Aβ deposition. In terms of AD pathophysiology, more attention needs to be paid to the role of LDL-C.