Abstract
BackgroundAlzheimer’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.MethodsWe 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.ResultsWe 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.ConclusionsThis 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.
Highlights
Alzheimer’s disease (AD) is a most common dementia in elderly people
Some symptoms of AD are similar to those of other neurodegenerative diseases, such as idiopathic normal pressure hydrocephalus. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) in the brain and causes gait disturbance, urinary incontinence, and dementia
First, we performed comprehensive metabolic analysis of the CSF to identify characteristic metabolites in the patients with AD and iNPH with the screening subjects indicated in Table 1
Summary
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. Nagata et al Biomarker Research (2018) 6:5 contrast to other dementias, iNPH is treatable by shunt operation that removes the accumulated CSF [3]. A precise diagnosis that discriminates patients with AD from patients with iNPH is essential for proper treatment at the early stages of these diseases. We tried to find additional biomarkers, capable of precisely detecting AD before neurodegeneration progresses
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