Distinct effects of cholesterol profile components on amyloid and vascular burdens

• Published in: Alzheimer's Research & Therapy 2023, Vol.15 (1)
• Main Authors: Kang, Sung Hoon, Yoo, Heejin, Cheon, Bo Kyoung, Park, Yu Hyun, Kim, Soo-Jong, Ham, Hongki, Jang, Hyemin, Kim, Hee Jin, Oh, Kyungmi, Koh, Seong-Beom, Na, Duk L, Kim, Jun Pyo, Seo, Sang Won
• Format: Report
• Language: English
• Subjects: Amyloid beta-protein; Blood cholesterol; Cerebrovascular disease; Cognition disorders; Health aspects; Measurement; Risk factors
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-023-01342-2

Background Cholesterol plays important roles in [beta]-amyloid (A[beta]) metabolism and atherosclerosis. However, the relationships of plasma cholesterol levels with A[beta] and cerebral small vessel disease (CSVD) burdens are not fully understood in Asians. Herein, we investigated the relationships between plasma cholesterol profile components and A[beta] and CSVD burdens in a large, non-demented Korean cohort. Methods We enrolled 1,175 non-demented participants (456 with unimpaired cognition [CU] and 719 with mild cognitive impairment [MCI]) aged [greater than or equal to] 45 years who underwent A[beta] PET at the Samsung Medical Center in Korea. We performed linear regression analyses with each cholesterol (low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c], and triglyceride) level as a predictor and each image marker (A[beta] uptake on PET, white matter hyperintensity [WMH] volume, and hippocampal volume) as an outcome after controlling for potential confounders. Results Increased LDL-c levels ([beta] = 0.014 to 0.115, p = 0.013) were associated with greater A[beta] uptake, independent of the APOE e4 allele genotype and lipid-lowering medication. Decreased HDL-c levels ([beta] = - 0.133 to - 0.006, p = 0.032) were predictive of higher WMH volumes. Increased LDL-c levels were also associated with decreased hippocampal volume (direct effect [beta] = - 0.053, p = 0.040), which was partially mediated by A[beta] uptake (indirect effect [beta] = - 0.018, p = 0.006). Conclusions Our findings highlight that increased LDL-c and decreased HDL-c levels are important risk factors for A[beta] and CSVD burdens, respectively. Furthermore, considering that plasma cholesterol profile components are potentially modified by diet, exercise, and pharmacological agents, our results provide evidence that regulating LDL-c and HDL-c levels is a potential strategy to prevent dementia. Keywords: LDL-c, HDL-c, [beta]-Amyloid-[beta] (A[beta]), White matter hyperintensity (WMH), Hippocampal volume