A probe for NIR-II imaging and multimodal analysis of early Alzheimer’s disease by targeting CTGF

Cao Lu, Cong Meng, Yuying Li, Jinling Yuan, Xiaojun Ren, Liang Gao, Dongdong Su, Kai Cao, Mengchao Cui, Qing Yuan () and Xueyun Gao ()
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Cao Lu: Beijing University of Technology
Cong Meng: Beijing University of Technology
Yuying Li: Beijing Normal University
Jinling Yuan: Beijing University of Technology
Xiaojun Ren: Beijing University of Technology
Liang Gao: Beijing University of Technology
Dongdong Su: Beijing University of Technology
Kai Cao: Beijing University of Technology
Mengchao Cui: Beijing Normal University
Qing Yuan: Beijing University of Technology
Xueyun Gao: Beijing University of Technology

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract To date, earlier diagnosis of Alzheimer’s disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aβ) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aβ plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.9 nM). 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 Aβ 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 Aβ plaque formation.

Date: 2024
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DOI: 10.1038/s41467-024-49409-4

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