Novel Compound For Screening, Imaging And Treating Alzheimer’s Disease

Highlights:

• New cyanine compound developed by scientists can be used to accurately screen for Alzheimer’s disease, as well as an imaging agent
• Compound has low toxicity and may also have therapeutic potential in Alzheimer’s disease
• Alzheimer’s disease is a common neurodegenerative disorder with no cure and current diagnostic methods may not be very effective and not entirely safe.

Newly discovered cyanine compounds found to have multiple uses as screening and imaging agents as well as with possible therapeutic potential. The compound has been invented by scientists at the Hong Kong Baptist University (HKBU) Chemistry. The invention has received four US patents as well as a patent by the Chinese government. The research team was headed jointly by Professor Ricky Wong Man-shing and Associate Professor Dr Li Hung-wing with faculty from the Department of Chemistry of HKBU.

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Cyanine Compounds as Screening Agent

Cyanine occurs in nature in blueberries, and the cyanine compounds employed by the team have been particularly suitable to detect amyloid.

• The proteins beta amyloid peptide, tau, and p-tau, in human's cerebrospinal fluid have been linked to Alzheimer's disease
• The proprietary cyanine compounds have been shown to accurately quantify these proteins when applied on a nanodetection screening test described below
• The screening test can be done on body fluids such as saliva, serum, and urine taking only very small amounts (few microliters). Normally, the protein is measured in the cerebrospinal fluid which is obtained by inserting a needle into the spinal cord, which is more risky.
• It is accurate, rapid, low cost and ultrasensitive in nature compared to existing tests

The Alzheimer’s protein (antigen) present in the body fluids will react with the corresponding antibody incorporated on the surface of magnetic nanoparticles. To this mixture the cyanine compound is added. If the protein is present, there will be enhancement of fluorescent signal which can be quantified on an ultraviolet imaging system.

Says Dr Li, "This newly developed assay will be particularly useful as a low-cost yet accurate diagnostic and prognostic tool for Alzheimer's disease. It can also serve as a novel alternative non-invasive tool for population-wide screening for the disease. This scientific detection assay has a high potential to serve as a practical diagnosis tool."

However, Li adds that the amounts of the protein in serum, urine and saliva is much lower than CSF, making detection more difficult.

The findings of the study titled "Ultra-sensitive detection of protein biomarkers for diagnosis of Alzheimer's disease" has appeared in the internationally respected academic journal Chemical Science 

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Cyanine Compounds as Imaging Agents

Interestingly, in yet another study, the team found one type of cyanine compound can specifically bind to short chains of beta-amyloid peptides (oligomers) and this binding results in enhancement of the fluorescent signal.

This unique property of cyanine compound can be applied to MRI and/or fluorescence imaging to detect beta-amyloid oligomers in the patient and to monitor disease status and progression.

It is these beta amyloid oligomers in the form of fibrils and senile plaques that are most neurotoxic and important in the pathogenesis of disease, making it all the more important to be able to detect them accurately than any other form of beta amyloid.  

The cyanine compound has in fact been successfully applied to detect and image beta-amyloid oligomers in Alzheimer’s disease transgenic mice models where the disease-like pathology has just started to evolve.

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Cyanine Compounds as Potential Treatment Option

It has also been shown that this newly created compound can cross the blood brain barrier, and is capable of preventing beta amyloid monomers from aggregating and forming neurotoxic oligomers and thus has a neuroprotective effect. In addition the compound displays low toxicity and its properties therefore show promise as a treatment option in Alzheimer’s disease that need to be further studied.

In fact the study team is currently looking at the neuroprotective effects of this compound on cognitive improvement in mouse model of Alzheimer’s disease.

Should future studies planned establish the efficacy of cyanine compounds in detecting, imaging and treatment of Alzheimer’s disease, it is indeed good news for patients and their families and doctors treating the disease.

Reference:

1. Yinhui Li, Di Xu, Anyang Sun, et al. Fluoro-substituted cyanine for reliable in vivo labelling of amyloid-β oligomers and neuroprotection against amyloid-β induced toxicity.Chemical ScienceDOI:10.1039/C7SC03974C

Source-Medindia