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Metabolome in progression to Alzheimer's disease
VTT Technical Research Centre of Finland, Espoo, Finland.ORCID iD: 0000-0002-2856-9165
Örebro University, School of Science and Technology. VTT Technical Research Centre of Finland, Espoo, Finland.
Department of Neurology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
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2011 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 1, article id e57Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2011. Vol. 1, article id e57
Keywords [en]
Alzheimer's disease; hypoxia; lipidomics; metabolomics; mild cognitive impairment; pentose phosphate pathway
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-59355DOI: 10.1038/tp.2011.55ISI: 000306217100001PubMedID: 22832349Scopus ID: 2-s2.0-83755180492OAI: oai:DiVA.org:oru-59355DiVA, id: diva2:1135881
Funder
EU, FP7, Seventh Framework Programme, 224328-PredictAD
Note

Funding Agencies:

Health Research Council of The Academy of Finland  121038 

EVO Grant from Kuopio University Hospital  5772709 

Available from: 2017-08-24 Created: 2017-08-24 Last updated: 2018-05-08Bibliographically approved

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Orešič, MatejHyötyläinen, Tuulia

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