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MODULATORY EFFECT OF BLOOD LDL CHOLESTEROL ON THE ASSOCIATION BETWEEN CEREBRAL AΒ AND TAU DEPOSITION IN OLDER ADULTS

S.M. Han, M.S. Byun, D. Yi, J.H. Jung, N. Kong, Y.Y. Chang, M. Keum, G.J. Jung, J.-Y. Lee, Y.-S. Lee, Y.K. Kim, K.M. Kang, C.-H. Sohn, D.Y. Lee, and for the KBASE Research Group

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 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, 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.

CITATION:
S.M. Han ; M.S. Byun ; D. Yi ; J.H. Jung ; N. Kong ; Y.Y. Chang ; M. Keum ; G.J. Jung ; J.-Y. Lee ; Y.-S. Lee ; Y.K. Kim ; K.M. Kang ; C.-H. Sohn ; D.Y. Lee ; and for the KBASE Research Group ; (2024): Modulatory Effect of Blood LDL Cholesterol on the Association between Cerebral Aβ and Tau Deposition in Older Adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.131

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