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Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (A\u03b2) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than A\u03b2 plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD\u2009~\u200921.9\u2009nM). The probe can well penetrate the blood-brain-barrier (BBB) of APP\/PS1 transgenic mice at early-stage (earlier than 3-month-old) in vivo, allowing non-invasive NIR-II imaging of CTGF when there is no appearance of A\u03b2 plaque deposition. Notably, this probe can also be applied to measuring CTGF on postmortem brain sections by multimodal analysis, including fluorescence imaging, peroxidase-like chromogenic imaging, and ICP-MS quantitation, which enables distinguishment between the brains of AD patients and healthy people. This probe possesses great potential for precise diagnosis of earlier AD before A\u03b2 plaque formation.<\/jats:p>","DOI":"10.1038\/s41467-024-49409-4","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T06:01:54Z","timestamp":1718172114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["A probe for NIR-II imaging and multimodal analysis of early Alzheimer\u2019s disease by targeting CTGF"],"prefix":"10.1038","volume":"15","author":[{"given":"Cao","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9337-345X","authenticated-orcid":false,"given":"Liang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-7864","authenticated-orcid":false,"given":"Mengchao","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-5931","authenticated-orcid":false,"given":"Qing","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-9945","authenticated-orcid":false,"given":"Xueyun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"49409_CR1","doi-asserted-by":"crossref","unstructured":"2023 Alzheimer\u2019s disease facts and figures. 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