Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-β42 and White Matter Microstructure in Cognitively Healthy Adults

Abstract

Background:Abnormal cholesterol metabolism changes the neuronal membrane and may promote amyloidogenesis. Oxysterols in cerebrospinal fluid (CSF) are related to Alzheimer’s disease (AD) biomarkers in mild cognitive impairment and dementia. Cholesterol turnover is important for axonal and white matter (WM) microstructure maintenance. Objective:We aim to demonstrate that the association of oxysterols, AD biomarkers, and WM microstructure occurs early in asymptomatic individuals. Methods:We studied the association of inter-individual variability of CSF 24-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-OHC), amyloid-β42 (Aβ42), total-tau (t-tau), phosphorylated-tau (p-tau), neurofilament (NfL), and WM microstructure using diffusion tensor imaging, generalized linear models and moderation/mediation analyses in 153 healthy adults. Results:Higher 7-KC levels were related to lower Aβ42, indicative of greater AD pathology (p = 0.041) . Higher 7-KC levels were related to lower fractional anisotropy (FA) and higher mean (MD), axial (AxD), and radial (RD) diffusivity. 7-KC modulated the association between AxD and NfL in the corpus callosum splenium (B = 39.39, p = 0.017), genu (B = 68.64, p = 0.000), and fornix (B = 10.97, p = 0.000). Lower Aβ42 levels were associated to lower FA and higher MD, AxD, and RD in the fornix, corpus callosum, inferior longitudinal fasciculus, and hippocampus. The association between AxD and Aβ42 was moderated by 7K-C (p = 0.048). Conclusion:This study adds clinical evidence to support the role of 7K-C on axonal integrity and the involvement of cholesterol metabolism in the Aβ42 generation process.

Publication DOI: https://doi.org/10.3233/JAD-200105
Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: © 2020 IOS Press. For Non-commercial use only
Publication ISSN: 1875-8908
Last Modified: 14 May 2024 07:14
Date Deposited: 27 Jul 2020 11:52
Full Text Link:
Related URLs: https://content ... sease/jad200105 (Publisher URL)
PURE Output Type: Article
Published Date: 2020-07-21
Published Online Date: 2020-06-06
Accepted Date: 2020-06-01
Authors: Iriondo, Ane
García-sebastian, Maite
Arrospide, Arantzazu
Arriba, Maria
Aurtenetxe, Sara
Barandiaran, Myriam
Clerigue, Montserrat
Ecay-torres, Mirian
Estanga, Ainara
Gabilondo, Alazne
Izagirre, Andrea
Saldias, Jon
Tainta, Mikel
Villanua, Jorge
Blennow, Kaj
Zetterberg, Henrik
Mar, Javier
Abad-garcía, Beatriz
Dias, Irundika H.k. (ORCID Profile 0000-0002-6620-8221)
Goñi, Felix M.
Martínez-lage, Pablo

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