Journal
JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 8, Pages 4053-4067Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00374
Keywords
Parkinson's disease; dementia; lipidomics; biomarkers; serum
Categories
Funding
- Natural Sciences and Engineering Research Council of Canada
- Canadian Institutes of Health Research (CIHR)
- Canada Research Chairs (CRC) program
- Genome Canada
- Alberta Innovates
- Canadian Consortium on Neurodegeneration in Aging (CCNA) - Alberta Innovates
- CIHR [MOP-67132]
- CRC program
- CCNA - CIHR
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This study focused on discovering biomarkers for Parkinson's disease (PD) and predicting the transition to dementia using untargeted lipidomics. The proposed biomarker panels showed excellent performance in differentiating PD patients from healthy controls and identifying PD patients at risk of developing dementia. Further research with a larger sample size is needed to validate these findings.
While a number of methods are available for analyzing lipids, unbiased untargeted lipidomics with high coverage remains a challenge. In this work, we report a study of isotope-standard-assisted liquid chromatography mass spectrometry lipidomics of serum for biomarker discovery. We focus on Parkinson's disease (PD), a neurodegenerative disorder that often progresses to dementia. Currently, the diagnosis of PD is purely clinical and there is limited ability to predict which PD patients will transition to dementia, hampering early interventions. We studied serum samples from healthy controls and PD patients with no clinical signs of dementia. A follow-up 3 years later revealed that a subset of PD patients had transitioned to dementia. Using the baseline samples, we constructed two biomarker panels to differentiate (1) PD patients from healthy controls and (2) PD patients that remained cognitively stable from PD patients with incipient dementia (diagnosed 3 years after sample collection). The proposed biomarker panels displayed excellent performance and may be useful for detecting prodromal PD dementia, allowing early interventions and prevention efforts. The biochemistry of significantly changed lipids is also discussed within the current knowledge of neurological pathologies. Our results are promising and future work using a larger cohort of samples is warranted.
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