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While alterations of specific DHA\u2010containing phospholipids have been described in the neocortex of patients with Alzheimer's disease (AD), the status of these lipids in dementia with Lewy bodies (DLB), known to manifest aggregated \u03b1\u2010synuclein\u2010containing Lewy bodies together with variable amyloid pathology, is unclear. In this study, post\u2010mortem samples from the parietal cortex of 25 DLB patients and 17 age\u2010matched controls were processed for phospholipidomics analyses using a liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) platform. After controlling for false discovery rate, six out of the 46 identified putative DHA\u2010phospholipid species were significantly decreased in DLB, with only one showing increase. Altered putative DHA\u2010phospholipid species were subsequently validated with further LC\u2013MS\/MS measurements. Of the DHA\u2010containing phospholipid (DCP) species showing decreases, five negatively correlated with soluble beta\u2010amyloid (A\u03b242) levels, whilst three also correlated with phosphorylated \u03b1\u2010synuclein (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Furthermore, five of these phospholipid species correlated with deficits of presynaptic Rab3A, postsynaptic neurogranin, or both (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Finally, we found altered immunoreactivities of brain lysolipid DHA transporter, MFSD2A, and the fatty acid binding protein FABP5 in DLB parietal cortex. In summary, we report alterations of specific DCP species in DLB, as well as their associations with markers of neuropathological burden and synaptopathology. These results support the potential role of DHA perturbations in DLB as well as therapeutic targets.<\/jats:p>","DOI":"10.1111\/bpa.13190","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T16:23:43Z","timestamp":1689697423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Decreased <scp>DHA<\/scp>\u2010containing phospholipids in the neocortex of dementia with Lewy bodies are associated with soluble A\u03b2<sub>42<\/sub>, phosphorylated \u03b1\u2010synuclein, and synaptopathology"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-0096","authenticated-orcid":false,"given":"Joyce R.","family":"Chong","sequence":"first","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine, National University of Singapore  Kent Ridge Singapore"},{"name":"Memory, Aging and Cognition Centre National University Health System  Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuek Ling","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine, National University of Singapore  Kent Ridge Singapore"},{"name":"Memory, Aging and Cognition Centre National University Health System  Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayang","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine, National University of Singapore  Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deron R.","family":"Herr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine, National University of Singapore  Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus R.","family":"Wenk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Yong Loo Lin School of Medicine, National University of Singapore  Kent Ridge Singapore"},{"name":"Singapore Lipidomics Incubator (SLING), Life Sciences Institute National University of Singapore  Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Francis","sequence":"additional","affiliation":[{"name":"College of Medicine and Health University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Ballard","sequence":"additional","affiliation":[{"name":"College of Medicine and Health University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Department of Old Age Psychiatry Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"},{"name":"Centre for Age\u2010Related Medicine Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Silver","sequence":"additional","affiliation":[{"name":"Signature Research Program in Cardiovascular and Metabolic Disorders Duke\u2010National University of Singapore (NUS) Medical School  Outram Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yong Loo Lin School of Medicine, National University of Singapore  Kent Ridge Singapore"},{"name":"Memory, Aging and Cognition Centre National University Health System  Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3050-634X","authenticated-orcid":false,"given":"Amaury","family":"Cazenave\u2010Gassiot","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Yong Loo Lin School of Medicine, National University of Singapore  Kent Ridge Singapore"},{"name":"Singapore Lipidomics Incubator (SLING), Life Sciences Institute National University of Singapore  Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7685-1424","authenticated-orcid":false,"given":"Mitchell K. 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