An international team of scientists has designed a new type of antibody that can accurately detect toxic polypolymers suspected to cause neurodegeneration associated with Alzheimer’s disease,media reported. The breakthrough promises to provide researchers with a new way to measure the accumulation of these proteins, improving drug design and clinical testing.
Treatments for Alzheimer’s disease have focused on eliminating toxic build-up of amyloid proteins, known as plaques. Recent studies have shown that major neurodegenerative damage associated with dementia and Alzheimer’s disease may occur earlier in time before these amyloid proteins form larger plaques.
The earliest stages of amyloid dysfunction in Alzheimer’s disease seem to be when these proteins begin to fold and clump incorrectly. When these misfolded proteins begin to gather together, they initially form so-called polymers. And these amyloid polymers can form more than a decade before larger plaques appear.
“There is an urgent need for quantitative methods to identify polymers — which play an important role in Alzheimer’s disease, but are too elusive for standard antibody detection strategies,” explains Michele Vendruscolo, lead researcher at the Misfolding Diseases Centre at the University of Cambridge. “Although amyloid hypothesis is a popular view, it has not been fully validated, in part because beta amyloid polymers are so difficult to detect that there are different opinions about the causes of Alzheimer’s disease. “
Using a decade-old method developed at the Folding Error Center, the researchers designed a new type of antibody that has a high degree of specific affinity for amyloid polymers, rather than any other form of amyloid. This allows researchers to quantify amyloid polymers with unprecedented accuracy.
“Polypolymers are difficult to detect, isolate, and study,” said Francesco Aprile, lead author of the study. “Our approach allows the production of antibody molecules that can target polymers, and although they are heterogeneous, we hope this could be an important step towards a new diagnostic approach. “
The breakthrough in the antibody did not immediately point to new treatments for Alzheimer’s disease, but researchers say better diagnostic monitoring of these polypolymers could greatly accelerate the development of new treatments. Clearly, testing these polymers will provide new insights into the efficacy of experimental drugs and help us understand the early stages of this destructive neurodegenerative disease.
“Therefore, the discovery of an antibody that can accurately target the polymer is an important step in monitoring disease progression, determining the cause and ultimately controlling the disease. Vendruscolo said.
The new study was published in the Proceedings of the National Academy of Sciences (PNAS).