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Metabolome in progr...
Metabolome in progression to Alzheimer's disease
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- Orešič, Matej, 1967- (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Hyötyläinen, Tuulia, 1971- (författare)
- Örebro universitet,Institutionen för naturvetenskap och teknik,VTT Technical Research Centre of Finland, Espoo, Finland
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- Herukka, S-K. (författare)
- Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland
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- Sysi-Aho, M. (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Mattila, I. (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Seppänan-Laakso, T. (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Julkunen, V. (författare)
- Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland
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- Gopalacharyulu, P. V. (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Hallikainen, M. (författare)
- Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland
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- Koikkalainen, J. (författare)
- VTT Technical Research Centre of Finland, Tampere, Finland
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- Kivipelto, M. (författare)
- Stockholms universitet,Karolinska Institutet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI)
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- Helisalmi, S. (författare)
- Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland
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- Lötjönen, J. (författare)
- VTT Technical Research Centre of Finland, Tampere, Finland
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- Soininen, H. (författare)
- Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
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(creator_code:org_t)
- 2011-12-13
- 2011
- Engelska.
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Ingår i: Translational Psychiatry. - New York : Nature Publishing Group. - 2158-3188. ; 1
- Relaterad länk:
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https://doi.org/10.1...
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https://www.nature.c...
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http://www.nature.co...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap -- Gerontologi, medicinsk/hälsovetenskaplig inriktning (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences -- Gerontology, specialising in Medical and Health Sciences (hsv//eng)
Nyckelord
- Alzheimer's disease; hypoxia; lipidomics; metabolomics; mild cognitive impairment; pentose phosphate pathway
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Orešič, Matej, 1 ...
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Hyötyläinen, Tuu ...
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Herukka, S-K.
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Sysi-Aho, M.
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Mattila, I.
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Seppänan-Laakso, ...
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Julkunen, V.
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Gopalacharyulu, ...
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Hallikainen, M.
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Koikkalainen, J.
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Kivipelto, M.
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Helisalmi, S.
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Lötjönen, J.
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Soininen, H.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Psykiatri
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Translational Ps ...
- Av lärosätet
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Örebro universitet
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Karolinska Institutet
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Stockholms universitet