title: The level of 24-Hydroxycholesteryl Esters is an Early Marker of Alzheimer's Disease.
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.
authors.affiliation: Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.affiliation: Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Fisciano (SA), Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dal Piaz
authors.affiliation: Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.|MAC Memory Center, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Ageing Sciences, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Iorio
authors.affiliation: TRASE S.R.L., Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Abrescia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002788:Cholesterol Esters / Q000097:blood*; D002853:Chromatography, Liquid; D060825:Cognitive Dysfunction / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000235:genetics; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D000073216:Mental Status and Dementia Tests; D008875:Middle Aged; D011379:Prognosis; D053719:Tandem Mass Spectrometry
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D002788:Cholesterol Esters
keywords: Alzheimer’s disease; biomarker; case control studies; cholesterol 
  esterification; cohort studies; mild cognitive impairment