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Here, we introduce the development of a hierarchical\u2010responsive therapeutic agent self\u2010assembled from phenylboronate ester\u2010linked Tjernberg's KLVFF peptide\u2010curcumin conjugates (CPKNAs), which is designed to dynamically track the spatiotemporal coordinates of biomarkers associated with AD heterogeneity in progression. The dynamic covalent phenylboronate ester bond undergoes varying degrees of dissociation in response to the temporal evolution patterns of amyloid\u2010\u03b2, reactive oxygen species, and glucose, three key indicators for staging AD progression, enabling self\u2010adaptive regulation of drug distribution and dosing tailored to specific phenotypes. Employing seven cellular models and three types of transgenic mice simulating different AD stages, we demonstrate that CPKNAs effectively minimize the risks of under\u2010 or overtreatment, achieving consistent therapeutic outcomes in mitigating cellular damage and improving brain dysfunction.<\/jats:p>","DOI":"10.1002\/adma.202516343","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:46:26Z","timestamp":1778057186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic Covalent Peptide\u2010Drug Conjugates Address the Heterogeneity in Alzheimer's Disease Progression"],"prefix":"10.1002","volume":"38","author":[{"given":"Yuheng","family":"Yang","sequence":"first","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory For Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wu","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory For Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Fan","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory For Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Yao","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory For Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory For Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Kang","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory For Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhe","family":"Tang","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory For Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjing","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomedical Imaging Science and System Paul C. 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