An observation study of urinary biomarker exploratory in Alzheimer's disease using high‐resolution mass spectrometry

Zhang, Qun; Wu, Shuo; Liu, Xinru; Yang, Jun; Dong, Xin; Zhou, Yunhua; Chen, Junjie; Li, Yamei; Yang, Jingzhi

doi:10.1002/bmc.5421

Cited by 7 publications

(8 citation statements)

References 54 publications

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“…However, according to instrument investigation, the resolution of a UHPLC-coupled OT instrument has been sacrificed in favor of achieving greater separation with higher acquisition rates (Kaufmann, 2018 ; de Souza et al, 2021 ). Furthermore, in line with our previous research on the discovery of AD urine metabolites, the OT systems for molecule detection displayed impressive stability performance (Zhang et al, 2022 ). Moreover, recent research that employs powerful bioinformatic techniques and high-throughput measurements of hundreds of metabolites has thoroughly documented the molecular alterations and disease-related pathways (Chandler et al, 2016 ; Sales et al, 2017 ; Uppal et al, 2017 ; Zhuang et al, 2021 ).…”

Section: Introductionsupporting

confidence: 77%

“…All study participants were fully informed of this research work, and written informed consent was obtained from all participants. The Alzheimer's Disease Assessment Scale—Cognitive (ADAS-Cog) Subscale test is a widely used cognitive test in research studies and clinical trials (Kueper et al, 2018 ; Zhang et al, 2022 ) and, therefore, was administered to evaluate the participants' recognition ability before the wet-lab experiments. Scores on the ADAS-Cog test range from 0 to 75, with a score above 18 indicating recognition impairment and leading to enrollment in the AD group.…”

Section: Methodsmentioning

confidence: 99%

“…The stepped normalized collision energy (NCE) consisted of 20%, 25%, and 30% for ion fragmentation, and the isolation window was narrowed to 1.0 m/z for improving the MS feature identification. MS injection order followed the previous batch sequence setting (Zhang et al, 2022 ). In brief, QC samples were placed at the beginning, in between the samples, and at the end of the whole batch to examine the stability of the MS method.…”

Section: Methodsmentioning

confidence: 99%

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Amyloid beta-correlated plasma metabolite dysregulation in Alzheimer's disease: an untargeted metabolism exploration using high-resolution mass spectrometry toward future clinical diagnosis

Yang

Wu²,

Yang³

et al. 2023

Front. Aging Neurosci.

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IntroductionAlzheimer's disease (AD) is a leading cause of dementia, and it has rapidly become an increasingly burdensome and fatal disease in society. Despite medical research advances, accurate recognition of AD remains challenging. Epidemiological evidence suggests that metabolic abnormalities are tied to higher AD risk.MethodsThis study utilized case-control analyses with plasma samples and identified a panel of 27 metabolites using high-resolution mass spectrometry in both the Alzheimer's disease (AD) and cognitively normal (CN) groups. All identified variables were confirmed using MS/MS with detected fragmented ions and public metabolite databases. To understand the expression of amyloid beta proteins in plasma, ELISA assays were performed for both amyloid beta 42 (Aβ42) and amyloid beta 40 (Aβ40).ResultsThe levels of plasma metabolites PAGln and L-arginine were found to significantly fluctuate in the peripheral blood of AD patients. In addition, ELISA results showed a significant increase in amyloid beta 42 (Aβ42) in AD patients compared to those who were cognitively normal (CN), while amyloid beta 40 (Aβ40) did not show any significant changes between the groups. Furthermore, positive correlations were observed between Aβ42/Aβ40 and PAGln or L-arginine, suggesting that both metabolites could play a role in the pathology of amyloid beta proteins. Binary regression analysis with these two metabolites resulted in an optimal model of the ROC (AUC = 0.95, p < 0.001) to effectively discriminate between AD and CN.DiscussionThis study highlights the potential of advanced high-resolution mass spectrometry (HRMS) technology for novel plasma metabolite discovery with high stability and sensitivity, thus paving the way for future clinical studies. The results of this study suggest that the combination of PAGln and L-arginine holds significant potential for improving the diagnosis of Alzheimer's disease (AD) in clinical settings. Overall, these findings have important implications for advancing our understanding of AD and developing effective approaches for its future clinical diagnosis.

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Section: Introductionsupporting

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Amyloid beta-correlated plasma metabolite dysregulation in Alzheimer's disease: an untargeted metabolism exploration using high-resolution mass spectrometry toward future clinical diagnosis

Yang

Wu²,

Yang³

et al. 2023

Front. Aging Neurosci.

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“…Targeted and untargeted metabolomics performed in brains of postmortem humans revealed that the phenylalanine metabolism is dysregulated in the hippocampus of these AD subjects . A recent observational study exploring urinary biomarkers for Alzheimer’s disease has shown upregulated N -phenylacetylglutamic acid among AD patients . In Alzheimer’s disease, increased levels of PAGln are found to be associated with impaired phospholipid and sphingolipid metabolism .…”

Section: Pagln In Neurological Disordersmentioning

confidence: 99%

“… 75 A recent observational study exploring urinary biomarkers for Alzheimer’s disease has shown upregulated N -phenylacetylglutamic acid among AD patients. 76 In Alzheimer’s disease, increased levels of PAGln are found to be associated with impaired phospholipid and sphingolipid metabolism. 77 In an untargeted metabolomics study among AD and mild cognitive impairment patients, high amounts of phenylacetic acid (PAA) are seen in saliva.…”

Section: Pagln In Neurological Disordersmentioning

confidence: 99%

Role of the Gut Bacteria-Derived Metabolite Phenylacetylglutamine in Health and Diseases

Krishnamoorthy,

Kalyan,

Hediyal

et al. 2024

ACS Omega

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Over the past few decades, it has been well established that gut microbiotaderived metabolites can disrupt gut function, thus resulting in an array of diseases. Notably, phenylacetylglutamine (PAGln), a bacterial derived metabolite, has recently gained attention due to its role in the initiation and progression of cardiovascular and cerebrovascular diseases. This meta-organismal metabolite PAGln is a byproduct of amino acid acetylation of its precursor phenylacetic acid (PAA) from a range of dietary sources like egg, meat, dairy products, etc. The microbiota-dependent metabolism of phenylalanine produces PAA, which is a crucial intermediate that is catalyzed by diverse microbial catalytic pathways. PAA conjugates with glutamine and glycine in the liver and kidney to predominantly form phenylacetylglutamine in humans and phenylacetylglycine in rodents. PAGln is associated with thrombosis as it enhances platelet activation mediated through the GPCRs receptors α2A, α2B, and β2 ADRs, thereby aggravating the pathological conditions. Clinical evidence suggests that elevated levels of PAGln are associated with pathology of cardiovascular, cerebrovascular, and neurological diseases. This Review further consolidates the microbial/biochemical synthesis of PAGln and discusses its role in the above pathophysiologies.

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Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases

Zhang

Dong²,

Bian³

et al. 2023

Fundamental Research

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An observation study of urinary biomarker exploratory in Alzheimer's disease using high‐resolution mass spectrometry

Cited by 7 publications

References 54 publications

Amyloid beta-correlated plasma metabolite dysregulation in Alzheimer's disease: an untargeted metabolism exploration using high-resolution mass spectrometry toward future clinical diagnosis

Amyloid beta-correlated plasma metabolite dysregulation in Alzheimer's disease: an untargeted metabolism exploration using high-resolution mass spectrometry toward future clinical diagnosis

Role of the Gut Bacteria-Derived Metabolite Phenylacetylglutamine in Health and Diseases

Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases

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