Investigating plasma and brain cholesterol esterification in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, with metabolic alterations, abnormal cholesterol and lipid levels in the bloodstream and central nervous system (CNS). Similar to plasma, cholesterol in the cerebrospinal fluid (CSF) is carried by lipoproteins known as "HDL-like particles," due to their close similarity in density and composition to plasma HDL. Lecithin cholesterol acyltransferase (LCAT) is a key enzyme in HDL metabolism, catalysing cholesterol esterification in both plasma and CSF, thus facilitating HDL maturation. This study aimed to investigate cholesterol esterification in plasma and CSF and to characterize HDL subclass distribution in patients with ALS. The study included 20 ALS patients and 20 controls, in whom lipoprotein profile and cholesterol esterification were evaluated in both plasma and CSF. Plasma lipid levels were similar between patients and controls; however, the amount of discoidal preβ-HDL was significantly reduced in ALS patients compared to controls (8.5±4.9% vs 13.6±4.1%, p<0.0001). A significant increase in CSF unesterified cholesterol levels was observed in ALS patients compared to controls (0.22±0.07 mg/dL vs 0.15±0.04 mg/dL, p<0.01), leading to an increased unesterified/total cholesterol ratio in ALS patients (0.52±0.12 vs 0.40±0.12, respectively). While plasma cholesterol esterification remained unchanged in ALS patients, the cholesterol esterification rate was significantly reduced in their CSF (0.12±0.08 vs 2.41±1.98, p<0.01), consistent with the previous data. In conclusion, these results suggest a hampered cholesterol esterification in the CSF of ALS patients. Whether this defect is related to the severity or progression of the disease remains to be defined.