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Here we present that MDK attenuates A\u03b2 assembly and influences amyloid formation in the 5xFAD amyloidosis mouse model. MDK protein mitigates fibril formation of both A\u03b240 and A\u03b242 peptides in Thioflavin T fluorescence assay, circular dichroism, negative stain electron microscopy, and NMR analysis. Knockout of\n                  <jats:italic>Mdk<\/jats:italic>\n                  gene in 5xFAD increases amyloid formation and microglial activation. Further comprehensive mass spectrometry-based profiling of whole proteome and detergent-insoluble proteome in these mouse models indicates significant accumulation of A\u03b2 and A\u03b2-correlated proteins, along with microglial components. Thus, our structural and mouse model studies reveal a protective role of MDK in counteracting amyloid pathology in Alzheimer\u2019s disease.\n                <\/jats:p>","DOI":"10.1101\/2025.03.20.644383","type":"posted-content","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T02:08:13Z","timestamp":1742695693000},"source":"Crossref","is-referenced-by-count":2,"title":["Midkine Attenuates A\u03b2 Fibril Assembly and Amyloid Plaque Formation"],"prefix":"10.64898","author":[{"given":"Masihuz","family":"Zaman","sequence":"first","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"},{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, St. Jude Children\u2019s Research 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