Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-β42 and White Matter Microstructure in Cognitively Healthy Adults
Open accessAbstract
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.
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These lipid species are known to accumulate with aging and AD.
“lipid species known to accumulate with aging and AD 32,55,56”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [56]
The Discussion (page unavailable) reports that CSF levels of 24-OHC and 27-OHC were higher in patients with AD or MCI in previous case-control studies, and that some other oxysterols were higher in early-stage AD brains than in controls. This supports an AD-related increase for some lipid species, but the paper does not say that these species accumulate with aging. (LLM, conf=0.87)
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- Authors
- Iriondo, A., García-Sebastian, M., Arrospide, A., Arriba, M., Aurtenetxe, S., Barandiaran, M., Clerigue, M., Ecay-Torres, M., Estanga, A., Gabilondo, A., Izagirre, A., Saldias, J., Tainta, M., Villanua, J., Blennow, K., Zetterberg, H., Mar, J., Abad-García, B., Dias, I. H. K., Goñi, F. M., & Martínez-Lage, P.
- Affiliations
- Fundacion CITA Alzheimer (ES)
- Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, Donostia-San Sebastian, Gipuzkoa, Spain
- Hospital Alto Deba (ES)
- University of the Basque Country (ES)
- Sahlgrenska University Hospital (SE)
- Central Analysis Service, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain
- Aston University (GB)
- Departamento de Bioquímica, University of the Basque Country (UPV/EHU) and Instituto Biofisika (CSIC, UPV/EHU), Leioa, Bizkaia, Spain
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2020-07-21
- Volume
- 76
- Issue
- 2
- Pages
- 643-656
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W3035314451
- Cited by
- 16
- References
- 57
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 1
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Aston Publications Explorer (Aston University) (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Eusko Jaurlaritza (RBFI-2015-1-0231)
- Ministerio de Economía y Competitividad
- Vetenskapsrådet (681712, 02532, 2013-2016, 2018-, ALFGBG-720931, 2018-02532)
- H2020 European Research Council (681712)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- 7-ketocholesterol, oxysterols
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cognition, Cross-Sectional Studies, Female, Humans, Ketocholesterols, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments, Cohort Studies, Biomarkers, Amyloid beta-Peptides, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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