engleski

Cerebrospinal fluid lipidomics in Alzheimer's disease

Many neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are associated with alteration of lipid metabolism (Wenk 2005, Abidhatla et al. 2006, Postle 2009). Despite the fact that evidences of lipid changes occurring in brain of AD patients have been published, only a few attempted to characterize the lipid profile of cerebrospinal fluid and dissect the potential differences in AD patients. Cerebrospinal fluid (CSF) is the most informative fluid source for neurodegenerative disease prognosis, due to constant physical contact with brain and is readily obtainable compared to tissues. Analysis of phospholipids and other lipids in CSF offers a high potential for lipid biomarker discovery, in neurological diseases (Han and Gross 2003, Postle 2009) and for understanding essential aspects of associated molecular processes. In this work we developed a high-throughput and sensitive method based on nanoHPLC/ESI QTOF MS for phospholipid screening in the CSF. We show that from a crude lipid extract (equivalent to 0.4 µl of CSF) we can easily detect and quantify different phosphatidylethanolamine, phosphatidylcholine, phosphatidlyinositol and sphingomyelin species. The developed method was used in a differential display study involving CSF samples of AD patients and non-demented controls, to conclude on its potential application in lipid biomarker discovery.

Alzheimer's disease; cerebrospinal fluid; lipids; mass spectrometry; phospholipids; sphingomyelin

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