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Despite extensive efforts have been devoted to developing fluorescent probes for A\u03b2 imaging, further improving the luminescent efficiency of prevailing probes still remains a significant challenge. Herein, we investigated the inner mechanism of constructing high\u2013efficient A\u03b2 probes via a structural cyclization strategy. Based on a typical donor\u2010acceptor A\u03b2 probe (Pro1), three cyclized derivatives (Pro2\u2010Pro4) are designed by incorporating dimethylene, trimethylene, and ethyleneoxy groups into the \u03c0\u2010conjugated bridge. It is found that all compounds exhibit high specificity at various binding sites within the A\u03b2 fibril, while Pro4 features preferable hydrogen bond interaction with the fibril. Notably, a significant enhanced fluorescence quantum efficiency is demonstrated in the ethyleneoxy\u2010contained counterpart, primarily due to the decreased nonradiative decay arising from the reduced nonadiabatic electronic coupling, electron\u2010vibration coupling, and vibrational modes mixing. Consequently, the newly designed compound Pro4 achieves both red\u2010shifted emission and optimal luminescent efficiency, making it a promising candidate for A\u03b2 imaging. These findings highlight the feasibility of structural cyclization as an effective approach to improve luminescent efficiency in A\u03b2\u2010targeted probes, contributing to the development of fluorescent imaging techniques for early AD diagnosis.<\/jats:p>","DOI":"10.1002\/chem.202502134","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:59:59Z","timestamp":1757408399000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cyclization Enhances Luminescence Efficiency of a Fluorescent Probe for Amyloid\u2010\u03b2 in Alzheimer's Disease"],"prefix":"10.1002","volume":"31","author":[{"given":"Xiaomeng","family":"Sun","sequence":"first","affiliation":[{"name":"International School for Optoelectronic Engineering School of Chemistry and Chemical Engineering Qilu University of Technology (Shandong Academy of Sciences)  Jinan 250353 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenshuo","family":"Chen","sequence":"additional","affiliation":[{"name":"International School for Optoelectronic Engineering School of Chemistry and Chemical Engineering Qilu University of Technology (Shandong Academy of Sciences)  Jinan 250353 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Shi","sequence":"additional","affiliation":[{"name":"International School for Optoelectronic Engineering School of Chemistry and Chemical Engineering Qilu University of Technology (Shandong Academy of Sciences)  Jinan 250353 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"International School for Optoelectronic Engineering School of Chemistry and Chemical Engineering Qilu University of Technology (Shandong Academy of Sciences)  Jinan 250353 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"International School for Optoelectronic Engineering School of Chemistry and Chemical Engineering Qilu University of Technology (Shandong Academy of Sciences)  Jinan 250353 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-3868","authenticated-orcid":false,"given":"Yujin","family":"Zhang","sequence":"additional","affiliation":[{"name":"International School for Optoelectronic Engineering School of Chemistry and Chemical Engineering Qilu University of Technology (Shandong Academy of Sciences)  Jinan 250353 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00823-3"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf5128"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq5252"},{"journal-title":"Nat. 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