Serum 24-hydroxycholesterol in probable Alzheimer's dementia: Reexploring the significance of a tentative Alzheimer's disease biomarker

Abstract

Objective: This study measured and analyzed the serum levels of 24-hydroxycholesterol in patients with probable Alzheimer's disease (AD) and age-/sex-matched controls. Methods: A case-control study involving 40 AD patients and 40 controls was performed at a tertiary neurological teaching hospital in eastern India. Blood and serum samples were collected for APOE genotyping and 24-hydroxycholesterol levels, respectively. Results: Serum 24-hydroxycholesterol was significantly lower in AD patients compared to controls (median concentration: controls, 47.14 ng/mL (interquartile range, 16.34); AD patients, 32.93 ng/mL (interquartile range, 9.45); P < 0.001) but showed no significant correlation with Mini Mental State Examination (MMSE) score in AD cases (r = −0.169, P = 0.298) or in controls (r = 0.18, P = 0.26). No statistically significant difference was observed between serum 24-hydroxycholesterol levels of the APOE4-positive and -negative subgroups in AD patients (P = 0.79). Findings were consistent and unchanged even when the ratio of serum 24-hydroxycholesterol to serum total cholesterol was considered. Conclusion: The decreased 24-hydroxycholesterol level in peripheral circulation in AD cases observed in the present study may suggest its role in AD pathogenesis. The lack of a clear correlation between serum levels of 24-hydroxycholesterol and MMSE score—a surrogate marker of AD severity—raises the question as to whether 24-hydroxycholesterol level declines with decreasing neuronal mass or whether the steroid continues to play a protective role.