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58 reviewsabstractArticle history:Introduction: Tracking spatial lipidomic changes during Alzheimer’s disease (AD) progression is crucialReceived 11 November 2024for elucidating the underlying mechanisms of the disease.Revised 25 July 2025Objectives: This study aims to investigate the spatial–temporal lipidomic alterations and their associatedAccepted 21 August 2025metabolic enzyme changes during AD progression.Available online xxxxMethods: The spatial lipidomic changes and corresponding alterations in metabolic enzymes during ADKeywords:progression in amyloid precursor protein/presenilin-1 (APP/PS1) mice were thoroughly analyzed using anadvanced ambient mass spectrometry imaging (MSI) technique, complemented by immunofluorescenceAlzheimer’s disease(IF) imaging.Ambient mass spectrometry imagingResults: Distinct lipidomic differences were observed between AD and wild-type (WT) mice in both theSpatial lipidomicshippocampus (HP) and thalamus (TH), with the TH region exhibiting more significant lipid changes thanSphingolipid metabolismthe HP. A total of 88 lipid species with age- and region-specific alterations were identified, primarilyGlycerolipid & glycerophospholipidmetabolismwithin the sphingolipid, glycerolipid, and glycerophospholipid metabolic pathways. These metabolicchanges were corroborated by IF imaging, which demonstrated spatial variations in the correspondingenzymes within the lipid metabolic pathways. Notably, a significant downregulation of hexosylceramides⁎ Corresponding author at: Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan410011, China.⁎⁎ Corresponding author.E-mail addresses: [email protected] (W. Peng), [email protected] (Q. Wu). 1 These authors contributed equally to this work. 2025 The Author(s). Published by Elsevier B.V. on behalf of Cairo University.This is an open access
