Human dementia with Lewy bodies brain shows widespread urea elevations

Melissa Scholefield (Lead), Stephanie Church, Sasha Philbert, Jingshu Xu, Stefano Patassini, Garth JS Cooper

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction
Several recent studies have uncovered the presence of widespread urea elevations in multiple neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease dementia (PDD), vascular dementia (VaD), and Huntington's disease (HD). However, it is currently unknown whether dementia with Lewy bodies also shows these alterations in urea. This study aimed to investigate if and where urea is perturbed in the DLB brain.

Methods
Tissues from ten brain regions were obtained from 20 diagnosed cases of DLB and 19 controls. Urea concentrations were measured using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Case–control differences were assessed by nonparametric Mann-Whitney U tests, and s-values, E-values, effect sizes, and risk ratios were determined for each brain region. The results were compared to those previously obtained for AD, PDD, VaD, and HD.

Results
As with other previously investigated dementia diseases, DLB shows widespread urea elevations, affecting all ten regions investigated in the current study; the degree of these elevations is lower than that seen in AD or PDD, similar to that seen in HD, and higher than that observed in VaD. The highest urea fold-change was observed in the pons and the lowest in the primary visual cortex.

Conclusion
Urea elevations appear to be a shared alterations across at least five neurodegenerative diseases, despite their many differences in clinical and neuropathological presentation. The cause and effects of this perturbation should be the focus of future studies, for its possible contributions to the pathology of these conditions.
Original languageEnglish
JournalParkinsonism & Related Disorders
Issue number107017
Publication statusPublished - 20 May 2024

Keywords

  • Urea
  • dementia with Lewy bodies (DLB)
  • Parkinson's disease dementia
  • Alzheimer's disease (AD)
  • Huntington's disease
  • Vascular dementia
  • Mass Spectrometry
  • LC-MS/MS
  • UHPLC-MS
  • Metabolomics

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