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

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.