Using neurolipidomics to identify phospholipid mediators of synaptic (dys)function in Alzheimer's Disease

FieldValue
dc.contributor.authorBennett, Steffany A.L.
dc.contributor.authorValenzuela, Nicolas
dc.contributor.authorXu, Hongbin
dc.contributor.authorFranko, Bettina
dc.contributor.authorFai, Stephen
dc.contributor.authorFigeys, Daniel
dc.date.accessioned2014-10-01T02:06:30Z
dc.date.available2014-10-01T02:06:30Z
dc.date.created2013
dc.date.issued2013
dc.identifier.citationBennett SAL, Valenzuela N, Xu H, Franko B, Fai S and Figeys D (2013) Using neurolipidomics to identify phospholipid mediators of synaptic (dys)function in Alzheimer's Disease. Front. Physiol. 4:168.
dc.identifier.urihttp://hdl.handle.net/10393/31665
dc.identifier.urihttp://journal.frontiersin.org/Journal/10.3389/fphys.2013.00168/abstract
dc.description.abstractNot all of the mysteries of life lie in our genetic code. Some can be found buried in our membranes. These shells of fat, sculpted in the central nervous system into the cellular (and subcellular) boundaries of neurons and glia, are themselves complex systems of information. The diversity of neural phospholipids, coupled with their chameleon-like capacity to transmute into bioactive molecules, provides a vast repertoire of immediate response second messengers. The effects of compositional changes on synaptic function have only begun to be appreciated. Here, we mined 29 neurolipidomic datasets for changes in neuronal membrane phospholipid metabolism in Alzheimer's Disease (AD). Three overarching metabolic disturbances were detected. We found that an increase in the hydrolysis of platelet activating factor precursors and ethanolamine-containing plasmalogens, coupled with a failure to regenerate relatively rare alkyl-acyl and alkenyl-acyl structural phospholipids, correlated with disease severity. Accumulation of specific bioactive metabolites [i.e., PC(O-16:0/2:0) and PE(P-16:0/0:0)] was associated with aggravating tau pathology, enhancing vesicular release, and signaling neuronal loss. Finally, depletion of PI(16:0/20:4), PI(16:0/22:6), and PI(18:0/22:6) was implicated in accelerating Aβ42 biogenesis. Our analysis further suggested that converging disruptions in platelet activating factor, plasmalogen, phosphoinositol, phosphoethanolamine (PE), and docosahexaenoic acid metabolism may contribute mechanistically to catastrophic vesicular depletion, impaired receptor trafficking, and morphological dendritic deformation. Together, this analysis supports an emerging hypothesis that aberrant phospholipid metabolism may be one of multiple critical determinants required for Alzheimer disease conversion.
dc.language.isoen
dc.titleUsing neurolipidomics to identify phospholipid mediators of synaptic (dys)function in Alzheimer's Disease
dc.typeArticle
dc.identifier.doi10.3389/fphys.2013.00168
CollectionPublications en libre accès financées par uOttawa // uOttawa financed open access publications

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