New cholesterol-derived molecules linked to Alzheimer’s

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Source: King’s College London.

Several molecules that are found in the blood and derived from cholesterol have improved our understanding of how Alzheimer’s disease develops, according to research carried out at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN).

The study showed that the presence of 10 identifiable molecules in the blood predicted Alzheimer’s with an accuracy of 79%, and six of these were esters that form during the breakdown of cholesterol in the body. It was funded by the Alzheimer’s Society and involved the analysis of blood samples from 124 individuals including 36 with Alzheimer’s disease and 48 with Mild Cognitive Impairment. The results could help to reveal new targets for drugs to treat the disease and, later down the line, may provide clues for the development of a technique that diagnoses Alzheimer’s at the early stages.

Dr Petroula Proitsi, Alzheimer’s Society Research Fellow at the Department of Basic and Clinical Neuroscience, IoPPN was the lead author on the study. She said: “The results of this study are very interesting as the identified metabolites are biochemically related to metabolites previously shown to be associated with Alzheimer’s. It will be very interesting to see whether changes in these metabolites are also associated with disease initiation and progression.”

The newly-identified molecules haven’t been link to Alzheimer’s before and so this research opens the door to further work on how they affect the disease as it progresses, and how the body’s processing of cholesterol may have an impact. Dr Doug Brown, Director of Research and Development at Alzheimer’s Society said: “Finding a way to detect Alzheimer’s before the disease takes hold would provide a huge step forward in the way we carry out research into the condition. This interesting study identifies a number of molecules connected to cholesterol which weren’t previously thought to be linked to Alzheimer’s and could be another piece in the jigsaw to helping us understand the condition.”

There is currently no cure for Alzheimer’s and the available treatments can only slow progress of the disease and relieve some of the symptoms. Dr Proitsi believes these results provide new clues about diagnosing the disease and tracing development but won’t provide new techniques or treatments by themselves:

“We would like to stress that these findings need to be expanded and replicated in larger cohorts. The false positive rate of 23.1% would mean that using these molecules for diagnosis would see nearly a quarter of healthy people wrongly diagnosed with Alzheimer’s. This highlights that these molecules cannot be used for diagnostic purposes and that the important message from this study is the identification of new interesting lipid molecules to be associated with Alzheimer’s disease.”

Paper reference: Proitsi, P. et al. ‘Plasma lipidomics analysis finds long chain cholesteryl esters to be associated with Alzheimer’s disease’ published in Translational Psychiatry DOI: 10.1038/tp.2014.127

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