Affiliations: [a] Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| [b] Department of Medicine and Surgery, University of Salerno, Fisciano (SA), Italy
| [c]
MAC Memory Center, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| [d] Department of Medical, Surgical, Neurological, Metabolic, and Ageing Sciences, Second University of Naples, Naples, Italy
| [e] TRASE S.R.L., Naples, Italy
Correspondence:
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Correspondence to: Roberta Ghidoni, Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, via Pilastroni 4, Brescia I-25125, Italy. Tel.: +39 030 3501725; Fax: +39 030 3533513; E-mail: [email protected].
Abstract: Cholesterol (C) brain accumulation seems to play a role in the Alzheimer’s disease (AD) pathogenesis. 24(S)-hydroxycholesterol (24OH-C) 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. Herein we analyzed the level of 24OH-C esters (% 24OH-CE) in i) cerebrospinal fluid (CSF) and homologous serum of AD (n = 13) and controls (n = 8); ii) plasma from AD (n = 30), controls (n = 30), mild cognitive impairment (MCI) converting to AD (n = 34), and stable MCI (n = 40). The % 24OH-CE in CSF positively correlated with that in homologous serum and was lower in both CSF and blood from AD patients as compared to controls; moreover, the plasma value of % 24OH-CE was lower in MCI conv-AD than in non-converters. Kaplan Meier Survival curves revealed a significant anticipation of the disease onset in AD and MCI conv-AD subjects with the lowest % 24OH-CE values. In conclusion, the reduction of % 24OH-CE in AD and MCI conv-AD, as well as the anticipation of the disease in patients with the lowest % 24OH-CE, support a role of the cholesterol/lecithin-cholesterol acyltransferase axis in AD onset/progression. Thus, targeting brain cholesterol metabolism could be a valuable strategy to prevent AD associated cognitive decline.
Keywords: Alzheimer’s disease, biomarker, case control studies, cholesterol
esterification, cohort studies, mild cognitive impairment
