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Abstract

Background: Neurodegenerative diseases remain a central topic in biomedical research, with Alzheimer’s disease (AD) being the most extensively studied. Recent advances in multi-omics integration, particularly proteomics-based approaches, have enabled a deeper understanding of AD-related molecular pathways and their interconnections. However, challenges such as data heterogeneity and the complexity of large-scale datasets continue to hinder comprehensive integration and model interpretation. Methods: A total of 792 publications were retrieved from PubMed, among which, 27 peer-reviewed studies from 2024 and 2025 focusing on proteomics-anchored multi-omics integration for AD were selected for detailed analysis. These papers were categorized based on their integration strategies, omics combinations, and analytical methodologies. Additionally, statistical analysis of 218 studies published in 2024–2025 was performed to identify dominant omics layers and common integration trends. Results: Proteomics emerged as the most frequently studied omics layer and was most often integrated with transcriptomics in AD multi-omics studies. The analysis also revealed recurrent machine learning methods used for feature extraction and integration, along with key biological pathways implicated in AD pathogenesis, including amyloid metabolism, synaptic function, and neuroinflammation. Conclusions: This review provides a systematic overview of recent trends in proteomics-based multi-omics integration for AD research. It highlights both the scientific advances and methodological limitations in current approaches, serving as a valuable reference for researchers seeking to refine analytical frameworks and design more interpretable, data-driven studies in neurodegenerative disease research.