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CSF metabolites ass...
CSF metabolites associated with biomarkers of Alzheimer's disease pathology
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Dong, R. C. (författare)
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Lu, Q. S. (författare)
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Kang, H. (författare)
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Suridjan, I. (författare)
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Kollmorgen, G. (författare)
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Wild, N. (författare)
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Deming, Y. (författare)
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Van Hulle, C. A. (författare)
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Anderson, R. M. (författare)
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- Zetterberg, Henrik, 1973 (författare)
- 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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- Blennow, Kaj, 1958 (författare)
- 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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Carlsson, C. M. (författare)
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Asthana, S. (författare)
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Johnson, S. C. (författare)
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Engelman, C. D. (författare)
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Frontiers in Aging Neuroscience. - 1663-4365. ; 15
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- IntroductionMetabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer's disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease.MethodsThe relative abundance of untargeted metabolites was assessed in 161 individuals from the Wisconsin Registry for Alzheimer's Prevention. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals from then Wisconsin Alzheimer's Disease Research Center. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study.ResultsMetabolome-wide association study results showed several significantly associated metabolites for all the biomarkers except A & beta;42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid & beta; (A & beta;40), & alpha;-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for A & beta;40 and & alpha;-synuclein.DiscussionThis study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer's disease
- metabolomics
- CSF NeuroToolKit biomarkers
- metabolome-wide association
- Mendelian randomization
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Dong, R. C.
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Lu, Q. S.
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Kang, H.
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Suridjan, I.
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Kollmorgen, G.
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Wild, N.
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visa fler...
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Deming, Y.
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Van Hulle, C. A.
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Anderson, R. M.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Carlsson, C. M.
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Asthana, S.
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Johnson, S. C.
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Engelman, C. D.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Frontiers in Agi ...
- Av lärosätet
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Göteborgs universitet