Study on Early Retinal Pathological Changes and Biological Mechanisms in AlCl3/D-gal-induced sporadic AD-like mouse model Based on TMT Proteomics

Objective To explore early differentially expressed proteins (DEPs) in the retina of sporadic Alzheimer’s disease (AD) mice using tandem mass tag (TMT)-based quantitative proteomics, and to elucidate the microscopic pathological changes and potential mechanisms underlying early retinal pathology. Methods Ninety KM mice were randomly divided into a model group and a control group (n = 45 per group). The model group was administered AlCl ₃ combined with D-galactose for 14 weeks to induce a sporadic AD-like mouse model. Behavioral tests were performed on 15 randomly selected mice from each group at weeks 6, 10, and 14. Optical coherence tomography (OCT) and electroretinography (ERG) assessed retinal structural and functional changes in each group. Retinal DEPs from mice at 6 weeks were identified by TMT proteomics and validated by Western blot analysis. DEPs were defined as proteins exhibiting a fold change > 1.2 or < 0.83, P < 0.05, and at least two unique peptides. Bioinformatics analyses were performed using Proteome Discoverer software with the integrated Sequest HT search engine. Results Compared to controls, mice in the model group exhibited short-term memory impairment and long-term learning and memory dysfunction at weeks 10 and 14, respectively. OCT indicated significantly reduced total retinal thickness, RNF + GC+IPL composite layer thickness, and ONL thickness in the model group at weeks 6, 10, and 14 (P < 0.01). ERG Trial registration Not applicable.