Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-ß42 and White Matter Microstructure in Cognitively Healthy Adults.
J Alzheimers Dis
; 76(2): 643-656, 2020.
Article
en En
| MEDLINE
| ID: mdl-32538843
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), 7ß-hydroxycholesterol (7ß-OHC), amyloid-ß42 (Aß42), 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 Aß42, indicative of greater AD pathology (pâ=â0.041) . 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 (Bâ=â39.39, pâ=â0.017), genu (Bâ=â68.64, pâ=â0.000), and fornix (Bâ=â10.97, pâ=â0.000). Lower Aß42 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 Aß42 was moderated by 7K-C (pâ=â0.048). CONCLUSION: This study adds clinical evidence to support the role of 7K-C on axonal integrity and the involvement of cholesterol metabolism in the Aß42 generation process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Cognición
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Sustancia Blanca
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Cetocolesteroles
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Países Bajos