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Routine liquid chromatography-mass spectrometry (LC-MS)-based large-scale lipidomic methods often fail to elucidate subtle yet important structural features such as\n                    <jats:italic>sn<\/jats:italic>\n                    -position, hindering the precise interrogation of GP molecules. Leveraging high-resolution demultiplexing (HRdm) ion mobility spectrometry (IMS), we develop a four-dimensional (4D) lipidomic strategy to resolve GP\n                    <jats:italic>sn<\/jats:italic>\n                    -position isomers. We further construct a comprehensive experimental 4D GP database of 498 GPs identified from the mouse brain and an in-depth extended 4D library of 2500 GPs predicted by machine learning, enabling automated profiling of GPs with detailed acyl chain\n                    <jats:italic>sn<\/jats:italic>\n                    -position assignment. Analyzing three mouse brain regions (hippocampus, cerebellum, and cortex), we successfully identify a total of 592 GPs including 130 pairs of\n                    <jats:italic>sn<\/jats:italic>\n                    -position isomers. Further temporal GPs analysis in the three functional brain regions illustrates their metabolic alterations in AD progression.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-50299-9","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T10:03:47Z","timestamp":1721815427000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Spatially and temporally probing distinctive glycerophospholipid alterations in Alzheimer\u2019s disease mouse brain via high-resolution ion mobility-enabled sn-position resolved lipidomics"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3294-4537","authenticated-orcid":false,"given":"Shuling","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9465-498X","authenticated-orcid":false,"given":"Zhijun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2989-9833","authenticated-orcid":false,"given":"Daniel G.","family":"Delafield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-2648","authenticated-orcid":false,"given":"Michael J.","family":"Rigby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-9541","authenticated-orcid":false,"given":"Gaoyuan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-417X","authenticated-orcid":false,"given":"Megan","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0259-8424","authenticated-orcid":false,"given":"Luigi","family":"Puglielli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0056-3869","authenticated-orcid":false,"given":"Lingjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"50299_CR1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/nrendo.2016.98","volume":"12","author":"X Han","year":"2016","unstructured":"Han, X. 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