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Conventional probes are designed to target the\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010sheet structures of mature fibrils and are thus blind to these transient, nonfibrillar species. Here, we introduce \u201csite\u2010ordered engineering\u201d strategy, a peptide\u2010conjugated QMFluors conjugate designed to selectively target A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    <jats:sub>1\u201342<\/jats:sub>\n                    monomers with high fidelity. We identified the conjugation site order on the fluorophore as the key parameter controlling this molecular topology and self\u2010assembly behavior. This breakthrough is enabled by a hydrogen\u2010bond\u2010driven recognition mechanism, fundamentally departing from classical dyes that target the\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010sheets of mature fibrils. This yields an unprecedented \u201cinverted selectivity\u201d with a 20\u2010fold fluorescence enhancement for monomers over fibrils. Using probe\n                    <jats:italic>N<\/jats:italic>\n                    \u2010QM\u2010KLVFF with super\u2010resolution microscopy, we reveal the nanoscale \u201ccore\u2010shell\u201d biophysical phase diagram of plaques, visualizing dense fibrillar cores surrounded by monomeric\/oligomeric halos. Furthermore, the probe demonstrates a limit of detection of pg\/mL level and excellent linearity, meeting the stringent requirements for trace cerebrospinal\u2010fluid\u2010biomarker analysis. This work provides not only a powerful tool for early diagnosis and pathological investigation, but also establishes \u201caggregation\u2010regulated accessibility\u201d as a generalizable principle for designing probes for other dynamic amyloid protein targets.\n                  <\/jats:p>","DOI":"10.1002\/anie.3711838","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:51:36Z","timestamp":1790812296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discriminating Monomers and Fibrils of Amyloid\u2010\n                    <i>\u03b2<\/i>\n                    <sub>1\u201342<\/sub>\n                    With Site\u2010Ordered Peptide\u2010QMFluors"],"prefix":"10.1002","author":[{"given":"Ruilong","family":"Dai","sequence":"first","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Dai","sequence":"additional","affiliation":[{"name":"China Bluestar Chengrand Co., Ltd.  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7130-769X","authenticated-orcid":false,"given":"Chenxu","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Bi","sequence":"additional","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peitao","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zhai","sequence":"additional","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology  Shanghai 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Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology  Shanghai China"},{"name":"State Key Laboratory of Green Chemical Engineering and Industrial Catalysis Center of Photosensitive Chemicals Engineering East China University of Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2192-825X","authenticated-orcid":false,"given":"Zhiqian","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic 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