Cholesterol metabolites and plant sterols in cerebrospinal fluid are associated with Alzheimer's cerebral pathology and clinical disease progression.

Détails

ID Serval
serval:BIB_7CB2F980F7D1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cholesterol metabolites and plant sterols in cerebrospinal fluid are associated with Alzheimer's cerebral pathology and clinical disease progression.
Périodique
The Journal of steroid biochemistry and molecular biology
Auteur⸱e⸱s
Jahn T., Clark C., Kerksiek A., Lewczuk P., Lütjohann D., Popp J.
ISSN
1879-1220 (Electronic)
ISSN-L
0960-0760
Statut éditorial
Publié
Date de publication
01/2021
Peer-reviewed
Oui
Volume
205
Pages
105785
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Altered cholesterol metabolism is associated with increased risk of neurodegeneration and in particular with the development of Alzheimer's disease (AD). Here, we investigate whether non-cholesterol sterols and oxysterols in the central nervous system are associated with (i) the presence of cerebral AD pathology, (ii) distinct aspects of AD pathology, i.e. amyloid pathology, neuronal injury, and tau pathology, and (iii) cognitive decline over time.
One hundred forty-two elder subjects with normal cognition, mild cognitive impairment, or mild dementia participating in a cohort study on cognitive decline and AD were included. Clinical and neuropsychological assessments were performed at inclusion and repeated at follow-up visits at 18 and 36 months. Concentrations of cholesterol, non-cholesterol sterols, and cholesterol metabolites were measured in cerebrospinal fluid (CSF), along with CSF beta-amyloid (Aβ) <sub>1-42</sub> ; Aβ <sub>1-42</sub> /Aβ <sub>1-40</sub> ratio, total-tau (tau), and tau phosphorylated at threonine 181 (p-tau) as markers of amyloid pathology, neuronal injury and tau pathology, respectively. Cognitive decline was assessed by changes in Mini-Mental State Examination and Clinical Dementia Rating sum of boxes at follow-up visits.
CSF 24S-hydroxycholesterol (24S-OHC) and the 24S-OHC/27-OHC ratio were higher in subjects with AD pathology. CSF desmosterol correlated with Aβ <sub>1-42</sub> levels. The 24S-OHC levels, the 24S-OHC/27-OHC ratio and the plant sterols campesterol and sitosterol were associated with the tau and p-tau levels. Both plant sterol concentrations along with the 24S-OHC/27-OHC ratio at baseline predicted cognitive decline at follow-up visits.
We show the importance of CSF levels of several non-cholesterol sterols and oxysterols to AD and core AD biomarkers. The plant sterols campesterol and sitosterol appear to be involved in tau pathology and neurodegeneration. CSF desmosterol level indicates CNS cholesterol synthesis and might be of relevance for clinical disease severity. Therefore these non-cholesterol sterols may represent intervention targets to slow down disease progression.
Mots-clé
Alzheimer’s disease, brain cholesterol metabolism, cerebrospinal fluid, cholesterol synthesis, lipids, neurodegeneration, oxysterols, Brain cholesterol metabolism, Cerebrospinal fluid, Cholesterol synthesis, Lipids, Neurodegeneration, Oxysterols
Pubmed
Web of science
Création de la notice
16/11/2020 15:30
Dernière modification de la notice
20/01/2021 7:26
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