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Longitudinal evalua...
Longitudinal evaluation of proton magnetic resonance spectroscopy metabolites as biomarkers in Huntington's disease
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Lowe, A. J. (författare)
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Rodrigues, F. B. (författare)
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Arridge, M. (författare)
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De Vita, E. (författare)
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Johnson, E. B. (författare)
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Scahill, R. I. (författare)
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Byrne, L. M. (författare)
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Tortelli, R. (författare)
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Heslegrave, A. (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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Wild, E. J. (författare)
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(creator_code:org_t)
- 2022-10-12
- 2022
- Engelska.
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:6
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The study by Lowe et al. uses magnetic resonance spectroscopy to investigate the biomarker potential of neurochemical metabolites in Huntington's disease. Cross-sectional associations were observed between metabolites and prognostic measures; however, the absence of consistent group differences and lack of clear longitudinal change indicates limited biomarker potential in Huntington's disease. Proton magnetic resonance spectroscopy is a non-invasive method of exploring cerebral metabolism. In Huntington's disease, altered proton magnetic resonance spectroscopy-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies are lacking. Proton magnetic resonance spectroscopy metabolites may represent a source of biomarkers, thus their relationship with established markers of disease progression require further exploration to assess prognostic value and elucidate pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardized collection of CSF, blood, phenotypic and volumetric imaging data, we used 3 T proton magnetic resonance spectroscopy in conjunction with the linear combination of model spectra method to quantify seven metabolites (total n-acetylaspartate, total creatine, total choline, myo-inositol, GABA, glutamate and glutathione) in the putamen of 59 participants at baseline (15 healthy controls, 15 premanifest and 29 manifest Huntington's disease gene expansion carriers) and 48 participants at 2-year follow-up (12 healthy controls, 13 premanifest and 23 manifest Huntington's disease gene expansion carriers). Intergroup differences in concentration and associations with CSF and plasma biomarkers; including neurofilament light chain and mutant Huntingtin, volumetric imaging markers; namely whole brain, caudate, grey matter and white matter volume, measures of disease progression and cognitive decline, were assessed cross-sectionally using generalized linear models and partial correlation. We report no significant groupwise differences in metabolite concentration at baseline but found total creatine and total n-acetylaspartate to be significantly reduced in manifest compared with premanifest participants at follow-up. Additionally, total creatine and myo-inositol displayed significant associations with reduced caudate volume across both time points in gene expansion carriers. Although relationships were observed between proton magnetic resonance spectroscopy metabolites and biofluid measures, these were not consistent across time points. To further assess prognostic value, we examined whether baseline proton magnetic resonance spectroscopy values, or rate of change, predicted subsequent change in established measures of disease progression. Several associations were found but were inconsistent across known indicators of disease progression. Finally, longitudinal mixed-effects models revealed glutamine + glutamate to display a slow linear decrease over time in gene expansion carriers. Altogether, our findings show some evidence of reduced total n-acetylaspartate and total creatine as the disease progresses and cross-sectional associations between select metabolites, namely total creatine and myo-inositol, and markers of disease progression, potentially highlighting the proposed roles of neuroinflammation and metabolic dysfunction in disease pathogenesis. However, the absence of consistent group differences, inconsistency between baseline and follow-up, and lack of clear longitudinal change suggests that proton magnetic resonance spectroscopy metabolites have limited potential as Huntington's disease biomarkers.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- biomarkers
- Huntington's disease
- magnetic resonance spectroscopy
- cerebrospinal fluid
- neurofilament light protein
- in-vivo
- cerebrospinal-fluid
- h-1-nmr
- spectroscopy
- energy-metabolism
- mr spectroscopy
- white-matter
- h-1 mrs
- brain
- repeat
- Neurosciences & Neurology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Lowe, A. J.
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Rodrigues, F. B.
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Arridge, M.
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De Vita, E.
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Johnson, E. B.
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Scahill, R. I.
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visa fler...
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Byrne, L. M.
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Tortelli, R.
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Heslegrave, A.
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Zetterberg, Henr ...
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Wild, E. J.
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visa färre...
- Om ämnet
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och Neurovetenskaper
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Göteborgs universitet