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

• Published in: Nature communications Vol. 15; no. 1; pp. 5000 - 15
• Main Authors: Lu, Cao, Meng, Cong, Li, Yuying, Yuan, Jinling, Ren, Xiaojun, Gao, Liang, Su, Dongdong, Cao, Kai, Cui, Mengchao, Yuan, Qing, Gao, Xueyun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 14/32; 14/34; 59/5; 631/1647/1888/1493; 631/1647/245/2225; 631/61/350/354; 64/60; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Biomarkers; Biomarkers - metabolism; Blood-brain barrier; Blood-Brain Barrier - diagnostic imaging; Blood-Brain Barrier - metabolism; Brain; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Connective tissue growth factor; Connective Tissue Growth Factor - metabolism; Connective tissues; Deposition; Diagnosis; Disease Models, Animal; Female; Gold; Gold - chemistry; Growth factors; Humanities and Social Sciences; Humans; Male; Medical imaging; Metal Nanoparticles - chemistry; Mice; Mice, Transgenic; multidisciplinary; Multimodal Imaging - methods; Nanoclusters; Neurodegenerative diseases; Neuroimaging; Optical Imaging - methods; Peroxidase; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - metabolism; Presenilin 1; Science; Science (multidisciplinary); Transgenic mice; β-Amyloid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-49409-4

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. Here the authors report an NIR-II gold probe for identification of early-stage AD. The probe enables non-invasive NIR-II imaging of elevated CTGF in brains of early AD mice and multimodally identifying AD patients’ brain sections before obvious Aβ deposition.