Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M111.274142
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dc.titleComparative lipidomic analysis of mouse and human brain with Alzheimer disease
dc.contributor.authorChan, R.B.
dc.contributor.authorOliveira, T.G.
dc.contributor.authorCortes, E.P.
dc.contributor.authorHonig, L.S.
dc.contributor.authorDuff, K.E.
dc.contributor.authorSmall, S.A.
dc.contributor.authorWenk, M.R.
dc.contributor.authorShui, G.
dc.contributor.authorDi Paolo, G.
dc.date.accessioned2014-12-12T07:10:16Z
dc.date.available2014-12-12T07:10:16Z
dc.date.issued2012-01-20
dc.identifier.citationChan, R.B., Oliveira, T.G., Cortes, E.P., Honig, L.S., Duff, K.E., Small, S.A., Wenk, M.R., Shui, G., Di Paolo, G. (2012-01-20). Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. Journal of Biological Chemistry 287 (4) : 2678-2688. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M111.274142
dc.identifier.issn00219258
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/115035
dc.description.abstractLipids are key regulators of brain function and have been increasingly implicated in neurodegenerative disorders including Alzheimer disease (AD). Here, a systems-based approach was employed to determine the lipidome of brain tissues affected by AD. Specifically, we used liquid chromatographymass spectrometry to profile extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late-onsetAD(LOAD) patients, as well as the forebrain of three transgenic familial AD (FAD) mouse models. Although the cerebellum lacked major alterations in lipid composition, we found an elevation of a signaling pool of diacylglycerol as well as sphingolipids in the prefrontal cortex of AD patients. Furthermore, the diseased entorhinal cortex showed specific enrichment of lysobisphosphatidic acid, sphingomyelin, the ganglioside GM3, and cholesterol esters, all of which suggest common pathogenic mechanisms associated with endolysosomal storage disorders. Importantly, a significant increase in cholesterol esters and GM3 was recapitulated in the transgenic FAD models, suggesting that these mice are relevant tools to study aberrant lipid metabolism of endolysosomal dysfunction associated with AD. Finally, genetic ablation of phospholipase D2, which rescues the synaptic and behavioral deficits of an FAD mouse model, fully normalizes GM3 levels. These data thus unmask a cross-talk between the metabolism of phosphatidic acid, the product of phospholipase D2, and gangliosides, and point to a central role of ganglioside anomalies in AD pathogenesis. Overall, our study highlights the hypothesis generating potential of lipidomics and identifies novel region-specific lipid anomalies potentially linked to AD pathogenesis. © 2012 by The American Society for Biochemistry and Molecular Biology Inc.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1074/jbc.M111.274142
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentLIFE SCIENCES INSTITUTE
dc.description.doi10.1074/jbc.M111.274142
dc.description.sourcetitleJournal of Biological Chemistry
dc.description.volume287
dc.description.issue4
dc.description.page2678-2688
dc.description.codenJBCHA
dc.identifier.isiut000300292300040
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