Dataset Information

Profiling of the cortical brain proteome in WT, KO, FAD and FAD/KO mice by TMT-LC/LC-MS/MS

ABSTRACT: Proteomic analysis of 5xFAD/Mdk-KO mouse brain reveals proteome-wide changes. This study investigates the impact of midkine (MDK) knockout in 5xFAD mouse model using comprehensive mass spectrometry-based whole proteome profiling. The data demonstrates significant alterations in amyloid formation and microglial activation, providing insights into MDK's protective role in Alzheimer's disease pathology.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Disease

SUBMITTER: ya huang

LAB HEAD: Junmin Peng

PROVIDER: PXD061103 | Pride | 2025-07-16

REPOSITORIES: Pride

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Publications

Midkine Attenuates Aβ Fibril Assembly and Amyloid Plaque Formation.

Zaman Masihuz M Yang Shu S Huang Ya Y Yarbro Jay M JM Hao Yanhong Y Wang Zhen Z Liu Danting D Harper Kiara E KE Soliman Hadeer H Hemphill Alex A Harvey Sarah S Pruett-Miller Shondra M SM Stewart Valerie V Tanwar Ajay Singh AS Kalathur Ravi R Grace Christy R CR Turk Martin M Chittori Sagar S Jiao Yun Y Wu Zhiping Z High Anthony A AA Wang Xusheng X Serrano Geidy E GE Beach Thomas G TG Yu Gang G Yang Yang Y Chen Ping-Chung PC Peng Junmin J

bioRxiv : the preprint server for biology 20250320

Proteomic profiling of Alzheimer's disease (AD) brains has identified numerous understudied proteins, including midkine (MDK), that are highly upregulated and correlated with Aβ since the early disease stage, but their roles in disease progression are not fully understood. Here we present that MDK attenuates Aβ assembly and influences amyloid formation in the 5xFAD amyloidosis mouse model. MDK protein mitigates fibril formation of both Aβ40 and Aβ42 peptides in Thioflavin T fluorescence assay, c ...[more]

PMID: 40166321

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Project description:Microglia are innate immune cells of the brain that perform phagocytic and inflammatory functions in disease conditions. Transcriptomic studies of acutely-isolated microglia have provided novel insights into their molecular and functional diversity in homeostatic and neurodegenerative disease states. State-of-the-art mass spectrometric methods can comprehensively characterize proteomic alterations in microglia in neurodegenerative disorders, potentially providing novel functionally-relevant molecular insights that are not provided by transcriptomics. However, proteomic profiling of adult primary microglia in neurodegenerative disease conditions has not been performed. We performed quantitative proteomic analyses of purified CD11b+ acutely-isolated microglia adult mice in normal, acute neuroinflammatory (LPS-treatment) and chronic neurodegenerative states (5xFAD model of Alzheimer’s disease [AD]) using tandem mass tag mass spectrometry. Differential expression analyses were performed to characterize specific microglial proteomic changes in 5xFAD mice and identify overlap with LPS-induced pro-inflammatory changes. Our results were also contrasted with existing proteomic data from wild-type mouse microglia and from existing microglial transcriptomic data from wild-type and 5xFAD mice. Neuropathological validation studies of select proteins were performed in human AD and 5xFAD brains. Of 4,133 proteins identified, 187 microglial proteins were differentially expressed in the 5xFAD mouse model of AD pathology, including proteins with previously known (Apoe, Clu and Htra1) as well as previously unreported relevance to AD biology (Cotl1 and Hexb). Proteins upregulated in 5xFAD microglia shared significant overlap with pro-inflammatory changes observed in LPS-treated mice. Several proteins increased in human AD brain were also upregulated by 5xFAD microglia (Aβ peptide, Apoe, Htra1, Cotl1 and Clu). Cotl1 was identified as a novel microglia-specific marker with increased expression and strong association with AD neuropathology. Apoe protein was also detected within plaque-associated microglia in which Apoe and Aβ were highly co-localized suggesting a role for Apoe in phagocytic clearance of Aβ. We report the first comprehensive comparative proteomic study of adult mouse microglia derived from acute neuroinflammatory and AD models, representing a valuable resource to the neuroscience research community. We highlight shared and unique microglial proteomic changes in acute neuroinflammatory, aging and AD mouse models in addition to identifying novel roles for microglial proteins in human neurodegeneration.

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	MDK_W1_F10.1.pepXML	Pepxml
	MDK_W1_F10.raw	Raw
	MDK_W1_F11.1.pepXML	Pepxml