Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025)
Abstract The advancements of proteomics technologies are shaping Alzheimer's disease (AD) research, revealing new molecular insights and improving biomarker discovery. Here, we summarize major AD proteomics studies since our 2021 review, focusing on disease mechanisms and biomarker identificati...
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BMC
2025-07-01
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| Series: | Molecular Neurodegeneration |
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| Online Access: | https://doi.org/10.1186/s13024-025-00874-5 |
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| author | Jay M. Yarbro Him K. Shrestha Zhen Wang Xue Zhang Masihuz Zaman Mengqi Chu Xusheng Wang Gang Yu Junmin Peng |
| author_facet | Jay M. Yarbro Him K. Shrestha Zhen Wang Xue Zhang Masihuz Zaman Mengqi Chu Xusheng Wang Gang Yu Junmin Peng |
| author_sort | Jay M. Yarbro |
| collection | DOAJ |
| description | Abstract The advancements of proteomics technologies are shaping Alzheimer's disease (AD) research, revealing new molecular insights and improving biomarker discovery. Here, we summarize major AD proteomics studies since our 2021 review, focusing on disease mechanisms and biomarker identification. Enhanced sensitivity and throughput in proteome profiling have been driven by mass spectrometry (MS)-based approaches and affinity-based platforms (e.g., Olink and SomaScan). Emerging techniques, including single-cell, spatial, and single-molecule proteomics, provide unprecedented resolution in studying cellular heterogeneity and pathological microenvironments (e.g., amyloidome). Multi-cohort analyses of AD brain tissues have revealed consensus protein alterations (n = 866), identifying novel disease-associated proteins validated in functional studies (e.g., MDK/PTN, NTN1, SMOC1, GPNMB, NPTX2, NRN1, VGF, and U1 snRNP). Proteomic studies of AD biofluids have identified distinct disease subtypes, offering candidate proteins for early detection. Comparisons between human tissues and AD mouse models highlight shared pathways in amyloid pathology while underscoring limitations in recapitulating human disease. Combining proteomics with genomics enables protein quantitative trait locus (pQTL) analysis in AD, linking genetic risk factors to protein expression changes. Discrepancies between proteome and transcriptome suggest altered protein turnover in AD. Overall, AD proteomics continues to provide mechanistic insights into disease progression and potential biomarkers for precision medicine. |
| format | Article |
| id | doaj-art-7d817a694de64fb1a0ffa83f2cbe3984 |
| institution | DOAJ |
| issn | 1750-1326 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Molecular Neurodegeneration |
| spelling | doaj-art-7d817a694de64fb1a0ffa83f2cbe39842025-08-20T03:06:05ZengBMCMolecular Neurodegeneration1750-13262025-07-0120111710.1186/s13024-025-00874-5Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025)Jay M. Yarbro0Him K. Shrestha1Zhen Wang2Xue Zhang3Masihuz Zaman4Mengqi Chu5Xusheng Wang6Gang Yu7Junmin Peng8Department of Structural Biology, St. Jude Children’s Research HospitalDepartment of Structural Biology, St. Jude Children’s Research HospitalDepartment of Structural Biology, St. Jude Children’s Research HospitalDepartment of Structural Biology, St. Jude Children’s Research HospitalDepartment of Structural Biology, St. Jude Children’s Research HospitalDepartment of Structural Biology, St. Jude Children’s Research HospitalDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science CenterDepartment of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical CenterDepartment of Structural Biology, St. Jude Children’s Research HospitalAbstract The advancements of proteomics technologies are shaping Alzheimer's disease (AD) research, revealing new molecular insights and improving biomarker discovery. Here, we summarize major AD proteomics studies since our 2021 review, focusing on disease mechanisms and biomarker identification. Enhanced sensitivity and throughput in proteome profiling have been driven by mass spectrometry (MS)-based approaches and affinity-based platforms (e.g., Olink and SomaScan). Emerging techniques, including single-cell, spatial, and single-molecule proteomics, provide unprecedented resolution in studying cellular heterogeneity and pathological microenvironments (e.g., amyloidome). Multi-cohort analyses of AD brain tissues have revealed consensus protein alterations (n = 866), identifying novel disease-associated proteins validated in functional studies (e.g., MDK/PTN, NTN1, SMOC1, GPNMB, NPTX2, NRN1, VGF, and U1 snRNP). Proteomic studies of AD biofluids have identified distinct disease subtypes, offering candidate proteins for early detection. Comparisons between human tissues and AD mouse models highlight shared pathways in amyloid pathology while underscoring limitations in recapitulating human disease. Combining proteomics with genomics enables protein quantitative trait locus (pQTL) analysis in AD, linking genetic risk factors to protein expression changes. Discrepancies between proteome and transcriptome suggest altered protein turnover in AD. Overall, AD proteomics continues to provide mechanistic insights into disease progression and potential biomarkers for precision medicine.https://doi.org/10.1186/s13024-025-00874-5Alzheimer’s diseaseNeurodegenerative diseasePathogenesisBiomarkerProteomicsProteome |
| spellingShingle | Jay M. Yarbro Him K. Shrestha Zhen Wang Xue Zhang Masihuz Zaman Mengqi Chu Xusheng Wang Gang Yu Junmin Peng Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025) Molecular Neurodegeneration Alzheimer’s disease Neurodegenerative disease Pathogenesis Biomarker Proteomics Proteome |
| title | Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025) |
| title_full | Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025) |
| title_fullStr | Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025) |
| title_full_unstemmed | Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025) |
| title_short | Proteomic landscape of Alzheimer’s disease: emerging technologies, advances and insights (2021 – 2025) |
| title_sort | proteomic landscape of alzheimer s disease emerging technologies advances and insights 2021 2025 |
| topic | Alzheimer’s disease Neurodegenerative disease Pathogenesis Biomarker Proteomics Proteome |
| url | https://doi.org/10.1186/s13024-025-00874-5 |
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