Metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study)
Abstract Alzheimer's disease (AD) is a progressive disease, and the number of AD patients is increasing every year as the population ages. One of the pathophysiological mechanisms of AD is thought to be the effect of metabolomic abnormalities. There have been several studies of metabolomic abno...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-19670-y |
| _version_ | 1797274490116243456 |
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| author | Tomoki Ozaki Yuta Yoshino Ayumi Tachibana Hideaki Shimizu Takaaki Mori Tomohiko Nakayama Kazuaki Mawatari Shusuke Numata Jun-ichi Iga Akira Takahashi Tetsuro Ohmori Shu-ichi Ueno |
| author_facet | Tomoki Ozaki Yuta Yoshino Ayumi Tachibana Hideaki Shimizu Takaaki Mori Tomohiko Nakayama Kazuaki Mawatari Shusuke Numata Jun-ichi Iga Akira Takahashi Tetsuro Ohmori Shu-ichi Ueno |
| author_sort | Tomoki Ozaki |
| collection | DOAJ |
| description | Abstract Alzheimer's disease (AD) is a progressive disease, and the number of AD patients is increasing every year as the population ages. One of the pathophysiological mechanisms of AD is thought to be the effect of metabolomic abnormalities. There have been several studies of metabolomic abnormalities of AD, and new biomarkers are being investigated. Metabolomic studies have been attracting attention, and the aim of this study was to identify metabolomic biomarkers associated with AD and mild cognitive impairment (MCI). Of the 927 participants in the Nakayama Study conducted in Iyo City, Ehime Prefecture, 106 were selected for this study as Control (n = 40), MCI (n = 26), and AD (n = 40) groups, matched by age and sex. Metabolomic comparisons were made across the three groups. Then, correlations between metabolites and clinical symptoms were examined. The blood mRNA levels of the ornithine metabolic enzymes were also measured. Of the plasma metabolites, significant differences were found in ornithine, uracil, and lysine. Ornithine was significantly decreased in the AD group compared to the Control and MCI groups (Control vs. AD: 97.2 vs. 77.4; P = 0.01, MCI vs. AD: 92.5 vs. 77.4; P = 0.02). Uracil and lysine were also significantly decreased in the AD group compared to the Control group (uracil, Control vs. AD: 272 vs. 235; P = 0.04, lysine, Control vs. AD: 208 vs. 176; P = 0.03). In the total sample, the MMSE score was significantly correlated with lysine, ornithine, thymine, and uracil. The Barthel index score was significantly correlated with lysine. The instrumental activities of daily living (IADL) score were significantly correlated with lysine, betaine, creatine, and thymine. In the ornithine metabolism pathway, the spermine synthase mRNA level was significantly decreased in AD. Ornithine was decreased, and mRNA expressions related to its metabolism were changed in the AD group compared to the Control and MCI groups, suggesting an association between abnormal ornithine metabolism and AD. Increased betaine and decreased methionine may also have the potential to serve as markers of higher IADL in elderly persons. Plasma metabolites may be useful for predicting the progression of AD. |
| first_indexed | 2024-03-07T14:59:07Z |
| format | Article |
| id | doaj.art-19f0f4c9b2fc420499c6e1e9fd4a76b5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T14:59:07Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-19f0f4c9b2fc420499c6e1e9fd4a76b52024-03-05T19:13:00ZengNature PortfolioScientific Reports2045-23222022-09-011211910.1038/s41598-022-19670-yMetabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study)Tomoki Ozaki0Yuta Yoshino1Ayumi Tachibana2Hideaki Shimizu3Takaaki Mori4Tomohiko Nakayama5Kazuaki Mawatari6Shusuke Numata7Jun-ichi Iga8Akira Takahashi9Tetsuro Ohmori10Shu-ichi Ueno11Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of MedicineDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of MedicineDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of MedicineDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of MedicineDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of MedicineDepartment of Psychiatry, Institute of Biomedical Science, Tokushima University Graduate SchoolDepartment of Preventive Environment and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Psychiatry, Institute of Biomedical Science, Tokushima University Graduate SchoolDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of MedicineDepartment of Preventive Environment and Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Psychiatry, Institute of Biomedical Science, Tokushima University Graduate SchoolDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of MedicineAbstract Alzheimer's disease (AD) is a progressive disease, and the number of AD patients is increasing every year as the population ages. One of the pathophysiological mechanisms of AD is thought to be the effect of metabolomic abnormalities. There have been several studies of metabolomic abnormalities of AD, and new biomarkers are being investigated. Metabolomic studies have been attracting attention, and the aim of this study was to identify metabolomic biomarkers associated with AD and mild cognitive impairment (MCI). Of the 927 participants in the Nakayama Study conducted in Iyo City, Ehime Prefecture, 106 were selected for this study as Control (n = 40), MCI (n = 26), and AD (n = 40) groups, matched by age and sex. Metabolomic comparisons were made across the three groups. Then, correlations between metabolites and clinical symptoms were examined. The blood mRNA levels of the ornithine metabolic enzymes were also measured. Of the plasma metabolites, significant differences were found in ornithine, uracil, and lysine. Ornithine was significantly decreased in the AD group compared to the Control and MCI groups (Control vs. AD: 97.2 vs. 77.4; P = 0.01, MCI vs. AD: 92.5 vs. 77.4; P = 0.02). Uracil and lysine were also significantly decreased in the AD group compared to the Control group (uracil, Control vs. AD: 272 vs. 235; P = 0.04, lysine, Control vs. AD: 208 vs. 176; P = 0.03). In the total sample, the MMSE score was significantly correlated with lysine, ornithine, thymine, and uracil. The Barthel index score was significantly correlated with lysine. The instrumental activities of daily living (IADL) score were significantly correlated with lysine, betaine, creatine, and thymine. In the ornithine metabolism pathway, the spermine synthase mRNA level was significantly decreased in AD. Ornithine was decreased, and mRNA expressions related to its metabolism were changed in the AD group compared to the Control and MCI groups, suggesting an association between abnormal ornithine metabolism and AD. Increased betaine and decreased methionine may also have the potential to serve as markers of higher IADL in elderly persons. Plasma metabolites may be useful for predicting the progression of AD.https://doi.org/10.1038/s41598-022-19670-y |
| spellingShingle | Tomoki Ozaki Yuta Yoshino Ayumi Tachibana Hideaki Shimizu Takaaki Mori Tomohiko Nakayama Kazuaki Mawatari Shusuke Numata Jun-ichi Iga Akira Takahashi Tetsuro Ohmori Shu-ichi Ueno Metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study) Scientific Reports |
| title | Metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study) |
| title_full | Metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study) |
| title_fullStr | Metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study) |
| title_full_unstemmed | Metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study) |
| title_short | Metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and Alzheimer’s disease (from the Nakayama Study) |
| title_sort | metabolomic alterations in the blood plasma of older adults with mild cognitive impairment and alzheimer s disease from the nakayama study |
| url | https://doi.org/10.1038/s41598-022-19670-y |
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