Abstract
| Original language | English |
|---|---|
| Article number | e57 |
| Number of pages | 9 |
| Journal | Translational Psychiatry |
| Volume | 1 |
| DOIs | |
| Publication status | Published - 2011 |
| MoE publication type | A1 Journal article-refereed |
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Keywords
- Alzheimer's disease
- hypoxia
- lipidomics
- metabolomics
- mild cognitive impairment
- pentose phosphate pathway
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Metabolome in progression to Alzheimer's disease. / Orešič, Matej (Corresponding Author); Hyötyläinen, Tuulia; Herukka, S.-K.; Sysi-Aho, Marko; Mattila, Ismo; Seppänen-Laakso, Tuulikki; Julkunen, V.; Gopalacharyulu, Peddinti; Hallikainen, M.; Koikkalainen, Juha; Kivipelto, M.; Helisalmi, S.; Lötjönen, Jyrki; Soininen, H.
In: Translational Psychiatry, Vol. 1, e57, 2011.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Metabolome in progression to Alzheimer's disease
AU - Orešič, Matej
AU - Hyötyläinen, Tuulia
AU - Herukka, S.-K.
AU - Sysi-Aho, Marko
AU - Mattila, Ismo
AU - Seppänen-Laakso, Tuulikki
AU - Julkunen, V.
AU - Gopalacharyulu, Peddinti
AU - Hallikainen, M.
AU - Koikkalainen, Juha
AU - Kivipelto, M.
AU - Helisalmi, S.
AU - Lötjönen, Jyrki
AU - Soininen, H.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - hypoxia
KW - lipidomics
KW - metabolomics
KW - mild cognitive impairment
KW - pentose phosphate pathway
U2 - 10.1038/tp.2011.55
DO - 10.1038/tp.2011.55
M3 - Article
VL - 1
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
M1 - e57
ER -