Modulatory Effect of Blood LDL Cholesterol on the Association between Cerebral Aβ and Tau Deposition in Older Adults

• Published in: The journal of prevention of Alzheimer's disease 2024, Vol.11 (6), p.1767-1774
• Main Authors: Han, S. M., Byun, M. S., Yi, D., Jung, J. H., Kong, N., Chang, Y. Y., Keum, M., Jung, G. J., Lee, J.-Y., Lee, Y.-S., Kim, Y. K., Kang, K. M., Sohn, C.-H., Lee, Dong Young
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - metabolism; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - metabolism; Brain - diagnostic imaging; Brain - metabolism; Cholesterol, LDL - blood; Cognitive Dysfunction - blood; Cognitive Dysfunction - metabolism; Cross-Sectional Studies; Female; Geriatrics/Gerontology; Humans; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Neurology; Original Research; Positron-Emission Tomography; Prospective Studies; Republic of Korea; tau Proteins - blood; tau Proteins - metabolism
• ISSN: 2426-0266; 2274-5807; 2426-0266
• DOI: 10.14283/jpad.2024.131

Background This study investigates the synergistic relationship between blood low-density lipoprotein cholesterol (LDL-C) and cerebral beta-amyloid (Aβ) in relation to tau deposition, a key factor in the pathology of Alzheimer’s disease (AD), in older adults across a diverse cognitive spectrum. Objectives To examine whether higher levels of LDL-C in the blood moderate the association of cerebral Aβ with tau deposition in older adults, including those with normal cognition, mild cognitive impairment, and Alzheimer’s disease dementia. Design Cross-sectional design. Setting: The study was conducted as a part of a prospective cohort study. All assessments were done at the Seoul National University Hospital, Seoul, South Korea. Participants: A total of 136 older adults (aged 60–85 years) with normal cognition, mild cognitive impairment or Alzheimer’s disease (AD) dementia were included. Measurements 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 There was a significant Aβ × 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, such as total cholesterol, high-density lipoprotein cholesterol, and triglycerides, did not show a similar moderation effect on the relationship between Aβ deposition and tau deposition. Conclusion Our findings suggest that blood LDL-C synergistically enhances the influence of Aβ deposition on tau pathology, emphasizing the need for greater attention to the role of LDL-C in AD progression.