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Detecting chiral molecules at concentrations relevant to disease states remains challenging. Herein, a new type of chiral gold nanostructure induced by D\u2010\/L\u2010cysteine\u2013leucine dipeptides with a\n                    <jats:italic>g<\/jats:italic>\n                    \u2010factor of 0.1 was successfully synthesized for enantiomer biomarker detection.\u00a0To enhance the discrimination performance, the chiral gold nanostructures were assembled into D\u2010\/L\u2010Au monolayers. As surface\u2010enhanced Raman scattering (SERS) substrates, the D\u2010\/L\u2010Au monolayers simultaneously deliver molecular structural specificity and enantioselectivity within a single spectrum, which can be a versatile, label\u2010free chiral discrimination strategy for the detection of D\u2010\/L\u2010kynurenine (Kyn). The mechanism was unveiled to involve high enantioselective adsorption energies between L\u2010 and D\u2010Kyn on the lattice plane (221), resulting in enantioselective sensing.\u00a0The results showed that the L\u2010Au monolayer reached a limit of detection (LOD) of 3.7\u00a0n\n                    <jats:sc>m<\/jats:sc>\n                    for L\u2010Kyn, while the D\u2010Au monolayer reached an LOD of 3.6\u00a0nM for D\u2010Kyn.\u00a0Notably, there was a significant difference in D\u2010Kyn levels between AD patients and healthy individuals in serum samples, a distinction not observed for L\u2010Kyn, which positioned D\u2010Kyn as a potential novel biomarker for clinical prediagnosis of AD patients, marking the first report of its kind worldwide.\u00a0This study provides a robust tool for advancing biomedical science and clinical diagnostics.\n                  <\/jats:p>","DOI":"10.1002\/anie.202502115","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T12:26:53Z","timestamp":1741696013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Chiral Gold Nanostructure Monolayers as SERS Substrates for Ultrasensitive Detection of Enantiomer Biomarkers of Alzheimer's Disease"],"prefix":"10.1002","volume":"64","author":[{"given":"Changlong","family":"Hao","sequence":"first","affiliation":[{"name":"International Joint Research Laboratory for Biointerface and Biodetection State Key Lab of Food Science and Technology School of Food Science and Technology Jiangnan University  Wuxi Jiangsu 214122 P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Wuxi Neurosurgical Institute Jiangnan University  Wuxi Jiangsu 214122 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Kuang","sequence":"additional","affiliation":[{"name":"International Joint Research Laboratory for Biointerface and Biodetection State Key Lab of Food Science and Technology School of Food Science and Technology Jiangnan University  Wuxi Jiangsu 214122 P.R. 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