A near‐infrared probe for detecting and interposing amyloid beta oligomerization in early Alzheimer's disease

Abstract

Background The misfolding and deposition of amyloid beta (Aβ) in human brain is the main hallmark of Alzheimer's disease (AD) pathology. One of the drivers of Alzheimer´s pathogenesis is the production of soluble oligomeric Aβ, which could potentially serve as a biomarker of AD. Methods Given that the diphenylalanine (FF) at the C‐terminus of Aβ fragments plays a key role in inducing the AD pathology, based on the hydrophobic structure of FF, we synthesized a near‐infrared BF2‐dipyrrolmethane fluorescent imaging probe (NB) to detect both soluble and insoluble Aβ. Results We found that NB not only binds Aβ, particularly oligomeric Aβ, but also interposes self‐assembly of Aβ through π‐π interaction between NB and FF. Conclusion This work holds great promise in the early detection of AD and may also provide an innovative approach to decelerate and even halt AD onset and progression.

Should artificial intelligence be used in conjunction with Neuroimaging in the diagnosis of Alzheimer’s disease?

“…A recent study developed the first NIRF probe that could image BACE1, a key protein in the pathogenic process, in live AD model mice (Bi et al, 2022). Future studies are looking to develop new NIRF probes for the diagnosis of Alzheimer's (Quan et al, 2023). Additionally, blood tests have shown promising data for replacing more invasive PET or CSF tests and will be further investigated (Veitch et al, 2022).…”

Small Molecular Fluorescent Probes for Alzheimer's Disease Associated Active Species

“…Wu group fabricated a new NIR fluorescent probe 29 (Figure 5) for detecting and interposing Aβ oligomerization in early AD model. [71] The design of the probe included a borondipyrromethene (BODIPY) fluorescent parent and two triphenylamine units. For free probe 29, the benzene ring could rotate freely within certain range, thus showing weak fluorescence.…”

Recent advances in small molecular near-infrared fluorescence probes for a targeted diagnosis of the Alzheimer disease

“…85 In a recent study, Wu et al developed a NIR probe NB for the imaging and therapy of A β oligomers with the mechanism as follows. 86 On the one hand, NB could specifically bind to A β oligomers, which led to the limitation in the rotation of benzene rings in the NB probe and caused 1650% times fluorescence enhancement (Fig. 3b).…”

“…In addition to the two widely studied pathological AD hallmarks including A β and NFTs in the aformentioned sections 4, other biomarkers such as viscosity, 127,128 reactive oxygen species, 41,86,129,130 reactive nitrogen species, 131 and hydrogen sulfide 132,133 have attracted increasing attention as well. It is mainly because these biomakers are aboundant in AD tissues, which brings in chances to achieve precise diagnosis.…”

“…Importantly, the probe could efficiently penetrate BBB and quickly reacted with local H 2 O 2 molecules in AD tissues, which assisted in achieving the precise monitoring of the A β -induced ROS level in a real-time manner. 86…”