What is it about?
Cholesterol accumulation in the brain seems to play a role in the Alzheimer’s disease (AD) pathogenesis. 24-hydroxycholesterol (24OH-C, also called cerebrosterol) is the predominant metabolite of brain C and its synthesis is believed to represent a way to remove excess C from neurons. Previous studies showed that 24OH-C level is altered in patients with neurodegenerative diseases, including AD. Only one study demonstrated that 24OH-C esterification is altered in neurodegenerative diseases, i.e. amyotrophic lateral sclerosis. In this work we found that level of 24OH-C esters in cerebrospinal fluid (CSF) positively correlated with that in homologous serum and was lower in both CSF and blood from AD patients as compared to controls. Then we analyzed the level of 24OH-C esters in plasma from AD, controls, and subjects with mild cognitive impairment (MCI) converting to AD (MCI-conv) or stable condition (i.e. MCI non-converters). The plasma level of 24OH-C esters was lower in MCI-conv than in non-converters. A significant anticipation of the AD onset was found in MCI-conv subjects with the lowest level of 24OH-C esters.
Why is it important?
The results indicate that reduced level of 24OH-C esters in AD and MCI-conv, as well as the disease anticipation in MCI-conv subjects with the lowest level, support a role of the cholesterol/LCAT axis in AD onset/progression.