Comparative analysis of cerebrospinal fluid metabolites in Alzheimer's disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

Yuki Nagata, Akiyoshi Hirayama, Satsuki Ikeda, Aoi Shirahata, Futaba Shoji, Midori Maruyama, Mitsunori Kayano, Masahiko Bundo, Kotaro Hattori, Sumiko Yoshida, Yu ichi Goto, Katsuya Urakami, Tomoyoshi Soga, Kouichi Ozaki, Shumpei Niida

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Alzheimer's disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. Methods: We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch's t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. Results: We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. Conclusions: This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.

Original languageEnglish
Article number5
JournalBiomarker Research
Volume6
Issue number1
DOIs
Publication statusPublished - 2018 Jan 22

Fingerprint

Normal Pressure Hydrocephalus
Cerebrospinal fluid
Metabolites
Cerebrospinal Fluid
Alzheimer Disease
ROC Curve
Dementia
Neurodegenerative diseases
Hydroxybutyrates
Capillary electrophoresis
Metabolomics
Capillary Electrophoresis
Urinary Incontinence
Gait
Regression analysis
Neurodegenerative Diseases
Serine
Mass spectrometry
Logistics
Early Diagnosis

Keywords

  • 2-hydroxybutyrate
  • Alzheimer's disease
  • Cerebrospinal fluid
  • Diagnostic marker
  • Glycerate
  • Idiopathic normal pressure hydrocephalus
  • N-acetylneuraminate
  • Serine

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer's disease and idiopathic normal pressure hydrocephalus in a Japanese cohort. / Nagata, Yuki; Hirayama, Akiyoshi; Ikeda, Satsuki; Shirahata, Aoi; Shoji, Futaba; Maruyama, Midori; Kayano, Mitsunori; Bundo, Masahiko; Hattori, Kotaro; Yoshida, Sumiko; Goto, Yu ichi; Urakami, Katsuya; Soga, Tomoyoshi; Ozaki, Kouichi; Niida, Shumpei.

In: Biomarker Research, Vol. 6, No. 1, 5, 22.01.2018.

Research output: Contribution to journalArticle

Nagata, Y, Hirayama, A, Ikeda, S, Shirahata, A, Shoji, F, Maruyama, M, Kayano, M, Bundo, M, Hattori, K, Yoshida, S, Goto, YI, Urakami, K, Soga, T, Ozaki, K & Niida, S 2018, 'Comparative analysis of cerebrospinal fluid metabolites in Alzheimer's disease and idiopathic normal pressure hydrocephalus in a Japanese cohort', Biomarker Research, vol. 6, no. 1, 5. https://doi.org/10.1186/s40364-018-0119-x
Nagata, Yuki ; Hirayama, Akiyoshi ; Ikeda, Satsuki ; Shirahata, Aoi ; Shoji, Futaba ; Maruyama, Midori ; Kayano, Mitsunori ; Bundo, Masahiko ; Hattori, Kotaro ; Yoshida, Sumiko ; Goto, Yu ichi ; Urakami, Katsuya ; Soga, Tomoyoshi ; Ozaki, Kouichi ; Niida, Shumpei. / Comparative analysis of cerebrospinal fluid metabolites in Alzheimer's disease and idiopathic normal pressure hydrocephalus in a Japanese cohort. In: Biomarker Research. 2018 ; Vol. 6, No. 1.
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abstract = "Background: Alzheimer's disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. Methods: We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch's t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. Results: We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. Conclusions: This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.",
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T1 - Comparative analysis of cerebrospinal fluid metabolites in Alzheimer's disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

AU - Nagata, Yuki

AU - Hirayama, Akiyoshi

AU - Ikeda, Satsuki

AU - Shirahata, Aoi

AU - Shoji, Futaba

AU - Maruyama, Midori

AU - Kayano, Mitsunori

AU - Bundo, Masahiko

AU - Hattori, Kotaro

AU - Yoshida, Sumiko

AU - Goto, Yu ichi

AU - Urakami, Katsuya

AU - Soga, Tomoyoshi

AU - Ozaki, Kouichi

AU - Niida, Shumpei

PY - 2018/1/22

Y1 - 2018/1/22

N2 - Background: Alzheimer's disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. Methods: We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch's t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. Results: We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. Conclusions: This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.

AB - Background: Alzheimer's disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. Methods: We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch's t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. Results: We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. Conclusions: This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.

KW - 2-hydroxybutyrate

KW - Alzheimer's disease

KW - Cerebrospinal fluid

KW - Diagnostic marker

KW - Glycerate

KW - Idiopathic normal pressure hydrocephalus

KW - N-acetylneuraminate

KW - Serine

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