Optical Method for the Diagnosis of Amyloid Diseases, A Biomarker Technology

The Technology
A spectroscopic, optical method for early detection of amyloid fibril formation in cerebrospinal fluid, as a non-destructive diagnostic tool for early detection of amyloid diseases.
The core recognition motif of Aβ peptide is the di-phenylalanine (FF) element, which has been found to self-assemble into nanostructures and Quantum Dots.  Similar structures have been observed in amyloid fibrils as well, an example below.
The amyloid structures are believed to have unique spectrums of optical absorption, photoluminescence, electroluminescence, injection luminescence, thermoluminescence, similar to those of the measured spectrums of self assembling Peptide Nanostructures. Such a distinct, concentration-sensitive measurement, can be used a biomarker for such diseases.

5-2013-459.jpg

The Need
There are at least 20 distinct human diseases that are associated with amyloid fibril formation: The most common and the most studied is Alzheimer’s disease, with a defined well known fibrils structure made of amyloid-β peptide (Aβ). A partial list of other amyloid diseases includes type II diabetes, amyloidosis, medullary carcinoma of the thyroid and prion diseases. The naturally self-assembled protein fibrils, associated with such neurodegenerative diseases are widely researched in the last century, however, an early, direct, non-dementia, diagnostic tool has not yet been found. 

Advantages
1. High concentration sensitivity due to a significant change in the optical properties of the oligomers and amyloid fibrils with their assembly which correlates to the disease progression.
2. The method can be applied for drugs assays against amyloid diseases for testing the drug potency to dissolve the amyloid fibrils.

Patents
US and EP patent applications WO 2010/038228.

Supporting Publications
1. Amdursky, N., Molotskii, M., Gazit, E., and Rosenman, G. (2009) Self-Assembled Bioinspired Quantum Dots: Optical Properties. Appl. Phys Lett. 94, 261907
2. Amdursky, N., Molotskii, M., Aronov, D., Adler-Abramovich, L., Gazit, E., and Rosenman, G. (2009) Blue Luminescence Based on Quantum Confinement at Peptide Nanotubes. Nano. Lett. 9, 3111-3115
3. Amdursky, N., Gazit E., and Rosenman, G. (2010) Quantum Confinement in Self-Assembled Bioinspired Peptide Hydrogels. Adv. Mater. 22, 2311-2315
4. Amdursky, N., Gazit, E., and Rosenman G. (2012) Formation of low-dimensional crystalline nucleus region during insulin amyloidogenesis process, Biochem. Biophys. Res. Commun. 419, 232-237