A Probe for NIR-II imaging and Multimodal Analysis of Early Alzheimer’s Disease by Targeting CTGF
Lu et al.
Nature Communications
DOI: 10.1038/s41467-024-49409-4
This recent publication in Nature Communications by researchers from Beijing University of Technology and Beijing Normal University showcases the use of a TOFWERK icpTOF 2R in combination with laser ablation for Alzheimer’s disease research.
Alzheimer’s disease is the most prevalent neurodegenerative disease worldwide. Accurate early diagnosis permits timely intervention, thereby delaying progression. Imaging of Amyloid-β (Aβ) plaque in the brain has been a hallmark of Alzheimer’s disease diagnosis; however, disappointing results from putative disease-modifying therapies targeting Aβ have diverted researchers’ attention to finding earlier biomarkers for Alzheimer’s disease . Recent studies revealed that elevated expression of connective tissue growth factor (CTGF) in the Alzheimer’s disease brain is strongly associated with the progression of clinical dementia and amyloid neuritic plaques (NP) and acts as an upstream regulator of Aβ plaque. Thus, CTGF could serve as an earlier diagnostic biomarker of Alzheimer’s disease than Aβ plaque.
To investigate the feasibility of this biomarker, the researchers developed a peptide-coated gold nanocluster that specifically targets CTGF with high affinity. This probe effectively penetrates the blood-brain barrier in APP/PS1 transgenic mice at an early stage, enabling non-invasive NIR-II imaging of CTGF before the appearance of amyloid-beta (Aβ) plaque deposition. Additionally, this probe can be utilized on postmortem brain sections for multimodal analysis to distinguish brains of healthy people and Alzheimer’s disease patients. This is done using fluorescence imaging, peroxidase-like chromogenic imaging, and laser ablation including inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) quantitation.
For LA-ICP-TOFMS analysis, Lu et al. analyzed the spatial distribution and expression level of CTGF in brain sections ex vivo using the icpTOF 2R coupled to an Iridia laser ablation system with a 193 nm ArF excimer laser and low dispersion ablation unit. This technique maps the gold signal from DGC-labeled CTGF on brain sections through a scanning method. To best visualize the distribution of DGC-labeled CTGF in the brain, sections from wild-type (WT) and 3-month-old APP/PS1 mice were collected, frozen with liquid nitrogen, and sectioned to 5 μm thickness. These sections were stained with DGC and analyzed using the LA-ICP-TOFMS system. Finally, the DGC in the brain sections was quantified by ICP-TOFMS.
This newly developed probe exhibits significant potential for the precise diagnosis of early-stage Alzheimer’s disease, preceding the formation of Aβ plaques. It can also be utilized for measuring CTGF in postmortem brain sections through multimodal analysis, including ICP-TOFMS quantitation using the icpTOF, allowing for the differentiation between the brains of Alzheimer’s disease patients and healthy individuals.
