{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:00:56Z","timestamp":1786122056188,"version":"build-2736575974"},"reference-count":144,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) involves not only amyloid-\u03b2 and tau pathology but also extensive disturbances in lipid metabolism, membrane organization, neuroinflammatory signaling, and tissue homeostasis. Conventional lipidomics has identified changes in phospholipids, sphingolipids, sulfatides, ceramides, gangliosides, and cholesterol-related pathways, but tissue homogenization removes their anatomical context. The aim of this review is to critically assess how matrix selection, sample preparation, ionization polarity, and emerging analytical strategies influence the detection and interpretation of spatial lipid alterations specifically associated with AD neuropathology. Current evidence shows that AD-related lipid remodeling is region- and lesion-specific, with recurrent findings including ganglioside accumulation, sulfatide depletion, ceramide-related alterations, phospholipid remodeling, lysosomal lipid changes, and disturbed cholesterol homeostasis within or around amyloid plaques. Matrix chemistry strongly influences lipid-class coverage, ionization efficiency, spectral background, adduct formation, spatial resolution, and biological interpretation. Matrix-Assisted Laser Desorption\/Ionization with Laser-Induced Post-Ionization (MALDI-2), ion mobility, reactive matrices, on-tissue derivatization, structural lipidomics, single-cell imaging, and spatial multiomics are expanding molecular coverage and annotation confidence. However, broader translation requires standardized workflows, structurally validated assignments, quantitative quality control, larger human cohorts, and improved interlaboratory reproducibility. Collectively, the available evidence indicates that the principal value of Matrix-Assisted Laser Desorption\/Ionization Mass Spectrometry Imaging (MALDI-MSI) in AD lies not merely in detecting altered lipid abundance, but in resolving lesion-specific lipid microenvironments whose interpretation depends directly on matrix chemistry, spatial resolution, and structural validation.<\/jats:p>","DOI":"10.3390\/ijms27167074","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T08:01:36Z","timestamp":1786089696000},"page":"7074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MALDI Mass Spectrometry Imaging in Alzheimer\u2019s Disease Lipidomics: Matrix Selection, Spatial Lipid Pathology and Emerging Analytical Strategies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-6570","authenticated-orcid":false,"given":"David","family":"Aebisher","sequence":"first","affiliation":[{"name":"Department of Photomedicine and Physical Chemistry, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Krzysztofi\u0144ska","sequence":"additional","affiliation":[{"name":"Medical Science Club, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Smolak","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging and Nuclear Medicine, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Bernat","sequence":"additional","affiliation":[{"name":"Medical Science Club, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktoria","family":"Czajka","sequence":"additional","affiliation":[{"name":"Medical Science Club, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Kowal","sequence":"additional","affiliation":[{"name":"Medical Science Club, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Kraso\u0144","sequence":"additional","affiliation":[{"name":"Medical Science Club, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6851-5869","authenticated-orcid":false,"given":"Klaudia","family":"Dynarowicz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and General Chemistry, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wies\u0142aw","family":"Guz","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging and Nuclear Medicine, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-5464","authenticated-orcid":false,"given":"Dorota","family":"Bartusik-Aebisher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and General Chemistry, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/febs.16344","article-title":"Lipid metabolism and Alzheimer\u2019s disease: Clinical evidence, mechanistic link and therapeutic promise","volume":"290","author":"Yin","year":"2023","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13024-025-00803-6","article-title":"Lipidome disruption in Alzheimer\u2019s disease brain: Detection, pathological mechanisms, and therapeutic implications","volume":"20","author":"He","year":"2025","journal-title":"Mol. 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