{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:18:09Z","timestamp":1794028689112,"version":"4.8.0"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"AbbVie","doi-asserted-by":"publisher","award":["13FH8I09IA"],"award-info":[{"award-number":["13FH8I09IA"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Amyloid-\u03b2 (A\u03b2) plaque deposits in the brain are a hallmark of Alzheimer\u2019s disease (AD) neuropathology. Plaques consist of complex mixtures of peptides like A\u03b21\u201342 and characteristic lipids such as gangliosides, and they are targeted by reactive microglia and astrocytes. Background: In pharmaceutical research and development, it is a formidable challenge to contextualize the different biomolecular classes and cell types of the A\u03b2 plaque microenvironment in a coherent experimental workflow on a single tissue section and on a benchtop imaging reader. Methods: Here, we developed a workflow that combines lipid MALDI mass spectrometry imaging using a vacuum-stable matrix with histopathology stains and with the MALDI HiPLEX immunohistochemistry of plaques and multiple protein markers on a benchtop imaging mass spectrometer. The three data layers consisting of lipids, protein markers, and histology could be co-registered and evaluated together. Results: Multimodal data analysis suggested the extensive co-localization of A\u03b2 plaques with the peptide precursor protein, with a defined subset of lipids and with reactive glia cells on a single brain section in APPPS1 mice. Plaque-associated lipids like ganglioside GM2 and phosphatidylinositol PI38:4 isoforms were readily identified using the tandem MS capabilities of the mass spectrometer. Conclusions: Altogether, our data suggests that complex pathology involving multiple lipids, proteins and cell types can be interrogated by this spatial multiomics workflow on a user-friendly benchtop mass spectrometer.<\/jats:p>","DOI":"10.3390\/ph18020252","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T09:05:42Z","timestamp":1739437542000},"page":"252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploring the A\u03b2 Plaque Microenvironment in Alzheimer\u2019s Disease Model Mice by Multimodal Lipid-Protein-Histology Imaging on a Benchtop Mass Spectrometer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4787-9513","authenticated-orcid":false,"given":"Elisabeth","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, 68163 Mannheim, Germany"},{"name":"Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-4090","authenticated-orcid":false,"given":"Thomas","family":"Enzlein","sequence":"additional","affiliation":[{"name":"Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, 68163 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Niemeyer","sequence":"additional","affiliation":[{"name":"Bruker Daltonics GmbH & Co. KG, 28359 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4074-2289","authenticated-orcid":false,"given":"Livia","family":"von Ammon","sequence":"additional","affiliation":[{"name":"Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, 68163 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Stumpo","sequence":"additional","affiliation":[{"name":"Bruker Scientific, LLC, Billerica, MA 01821, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Biber","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH & Co. KG, 67061 Ludwigshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4241-3284","authenticated-orcid":false,"given":"Corinna","family":"Klein","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH & Co. KG, 67061 Ludwigshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0802-6451","authenticated-orcid":false,"given":"Carsten","family":"Hopf","sequence":"additional","affiliation":[{"name":"Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, 68163 Mannheim, Germany"},{"name":"Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany"},{"name":"Mannheim Center for Translational Neurosciences (MCTN), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/s43587-023-00404-2","article-title":"Towards a Future Where Alzheimer\u2019s Disease Pathology Is Stopped before the Onset of Dementia","volume":"3","author":"Smets","year":"2023","journal-title":"Nat. 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