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Nanosensors for the diagnosis of Alzheimer's disease

Accumulating evidence unveils a role for protein misfolding in various diseases. To facilitate diagnosis, European researchers generated a powerful new tool that detects protein conformational activity in living cells.
Nanosensors for the diagnosis of Alzheimer's disease
Under physiological conditions, each protein has a predetermined three-dimensional structure that is central to their function. There are, however, cases when proteins misfold into abnormal structures causing various pathologies. Alzheimer's disease is one such example, caused by the misfolding of the peptide amyloid beta into fibrils and plaques that aggregate in patient brains. Detection of these misfolded peptides through a highly sensitive approach would facilitate prompt disease diagnosis.

Scientists on the EU-funded PROTEPROBE (Electrically Controlled Protein Conformation on 3D Tissue Scaffolds) project set out to develop a combinatorial technique for detecting protein folding changes. They used silver nanoplate biosensors to optically detect protein folding and conformation, and organic electrochemical transistors to record changes.

As proof of principle of this novel technique, researchers successfully implemented the prototype system for the detection of fibronectin in living cells and serum. Using this system, they could clearly discriminate between diffusely bound fibronectin and growing fibrils in an evolving extra cellular matrix.

Detecting tumour necrosis factor alpha (TNFα) is important as it is prevalent in brain function as well as in the onset of brain seizures. A significant achievement of the project was the implementation of a system to detect the small TNFα cytokine. This was achieved using nanoplates functionalised with antibodies against TNFα. Impressive was the fact that serum detection levels were as low as 6 pg/ml.

Collectively, the PROTEPROBE sensor offered beyond the state of the art detection of protein conformation. Its capacity to discriminate between the different protein structures renders it an invaluable tool for the diagnosis of diseases associated with protein misfolding.

Related information


Alzheimer's disease, nanoplate, electrochemical transistors, fibronectin, TNFα
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