Case-control study reveals 27-hydroxycholesterol metabolism disorders and CYP27A1 variants correlate with mild cognitive impairment, indicating cholesterol pathways influence early neurodegeneration.
SCOPE: The aim of the study is to investigate the relationship between 27-hydroxycholesterol (27-OHC), 27-hydroxylase (CYP27A1) polymorphisms, and Alzheimer's disease (AD). METHODS AND RESULTS: A case-control study based on EMCOA study includes 220 healthy cognition and mild cognitive impairment (MCI) subjects respectively, matched by sex, age, and education. The level of 27-OHC and its related metabolites are examined by high performance liquid chromatography-mass spectrometry (HPLC-MS). The results show that 27-OHC level is positively associated with risk of MCI (p < 0.001), negatively associated with specific domain of cognitive function. Serum 27-OHC is positively associated with 7a-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA) in cognitive healthy subjects, while positively associated with 3β-hydroxy-5-cholestenoic acid (27-CA) in MCI subjects (p < 0.001). CYP27A1 and Apolipoprotein E (ApoE) single nucleotide polymorphisms (SNPs) genotyping are determined. The global cognitive function is significant higher in Del-carrier of rs10713583, compared with AA genotype (p = 0.007). Stroop Color-Word Test Interference Trial (SCWT-IT) is significant higher in G-carrier genotype (p = 0.042), compared with TT genotype in rs12614206. CONCLUSIONS: The results show that 27-OHC metabolic disorder is associated with MCI and multi-domain cognitive function. CYP27A1 SNPs is correlated to cognitive function, while the interaction between 27-OHC and CYP27A1 SNPs need further study.
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Wang et al. (2023) studied this question.
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