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Cerebrospinal Fluid...
Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-beta(42) and White Matter Microstructure in Cognitively Healthy Adults
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Iriondo, A. (author)
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Garcia-Sebastian, M. (author)
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Arrospide, A. (author)
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Arriba, M. (author)
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Aurtenetxe, S. (author)
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Barandiaran, M. (author)
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Clerigue, M. (author)
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Ecay-Torres, M. (author)
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Estanga, A. (author)
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Gabilondo, A. (author)
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Izagirre, A. (author)
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Saldias, J. (author)
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Tainta, M. (author)
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Villanua, J. (author)
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Mar, J. (author)
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Abad-Garcia, B. (author)
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Dias, I. H. K. (author)
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Goni, F. M. (author)
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Martinez-Lage, P. (author)
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(creator_code:org_t)
- IOS Press, 2020
- 2020
- English.
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 76:2, s. 643-656
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Abstract
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- 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), 7 beta-hydroxycholesterol (7 beta-OHC), amyloid-beta(42) (A beta(42)), 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 A beta(42), 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 A beta(42) 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 A beta(42) 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 A beta(42) generation process.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- white matter
- oxysterols
- diffusion tensor imaging
- cerebrospinal fluid
- Amyloid-13
- amyloid-beta
- cholesterol-metabolism
- alzheimers-disease
- serum-cholesterol
- diffusion
- integrity
- oxysterols
- 24s-hydroxycholesterol
- localization
- dementia
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Iriondo, A.
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Garcia-Sebastian ...
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Arrospide, A.
-
Arriba, M.
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Aurtenetxe, S.
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Barandiaran, M.
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show more...
-
Clerigue, M.
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Ecay-Torres, M.
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Estanga, A.
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Gabilondo, A.
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Izagirre, A.
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Saldias, J.
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Tainta, M.
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Villanua, J.
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Blennow, Kaj, 19 ...
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Zetterberg, Henr ...
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Mar, J.
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Abad-Garcia, B.
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Dias, I. H. K.
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Goni, F. M.
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Martinez-Lage, P ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Alzhe ...
- By the university
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University of Gothenburg