Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease

Jericha Mill; Vihar Patel; Ozioma Okonkwo; Lingjun Li; Thomas Raife

doi:10.1016/j.jpha.2021.07.005

Volume 12 Issue 1

Feb. 2022

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Jericha Mill, Vihar Patel, Ozioma Okonkwo, Lingjun Li, Thomas Raife. Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease[J]. Journal of Pharmaceutical Analysis, 2022, 12(1): 178-185. doi: 10.1016/j.jpha.2021.07.005

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Jericha Mill, Vihar Patel, Ozioma Okonkwo, Lingjun Li, Thomas Raife. Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease[J]. Journal of Pharmaceutical Analysis, 2022, 12(1): 178-185. doi: 10.1016/j.jpha.2021.07.005

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Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease

doi: 10.1016/j.jpha.2021.07.005

a. Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA;
b. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA;
c. Clinical Science Center, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA;
d. School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA

Funds:

This research was supported in part by the National Institutes of Health (NIH) (Grant No.: RF1AG052324). Jericha Mill acknowledges a predoctoral traineeship supported by the NIH T32 training grant on Biology of Aging and Age-related Diseases (Grant No.: T32AG000213). Lingjun Li acknowledges a Vilas Distinguished Achievement Professorship and Charles Melbourne Johnson Distinguished Chair Professorship with funding provided by the Wisconsin Alumni Research Foundation and School of Pharmacy, University of Wisconsin-Madison.

Received Date: Jul. 07, 2020
Accepted Date: Jul. 13, 2021
Rev Recd Date: Jun. 08, 2021
Publish Date: Jul. 14, 2021

Abstract

Abstract

Diagnosing Alzheimer's disease (AD) in the early stage is challenging. Informative biomarkers can be of great value for population-based screening. Metabolomics studies have been used to find potential biomarkers, but commonly used tissue sources can be difficult to obtain. The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD. Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue, erythrocytes are plentiful and easily accessed. Moreover, erythrocytes are metabolically active, a feature that distinguishes this sample source from other bodily fluids like plasma and urine. In this preliminary pilot study, the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD (control (CTRL)) were compared. Whole blood was collected post-mortem and erythrocytes were analyzed using ultra-performance liquid chromatography tandem mass spectrometry. Over 750 metabolites were identified in AD and CTRL erythrocytes. Seven were increased in AD while 24 were decreased (P<0.05). The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism. Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients. Sphingolipids have been previously implicated in AD and other neurological conditions. Furthermore, previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal, healthy adults. Together, these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.
- Alzheimer's disease,
- Neurodegenerative disease,
- Mass spectrometry,
- Erythrocytes,
- Biomarkers,
- Metabolomics

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References(43)

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