An antibody has been designed that can identify the toxic particles that destroy healthy brain cells in Alzheimer’s disease, it has been announced.
Designed by a team from the University of Cambridge, University College London, UK, and Lund University, Sweden, the antibody is highly accurate at detecting toxic oligomers and quantifying their numbers.
Writing in the latest edition of Proceedings of the National Academy of Sciences (PNAS), the researchers say the discovery of an antibody to accurately target oligomers is an important step to monitor the disease, identify its cause, and control it.
Lead researcher Professor Michele Vendruscolo from Cambridge’s Centre for Misfolding Diseases, said: “There is an urgent unmet need for quantitative methods to recognise oligomers, which play a major role in Alzheimer’s disease, but are too elusive for standard antibody discovery strategies.
“Through our innovative design strategy, we have now discovered antibodies to recognise these toxic particles.”
Oligomers have been identified as the most likely cause of dementia. Although proteins are normally responsible for important cell processes, according to the amyloid hypothesis, but when people have Alzheimer’s disease proteins, including specifically amyloid-beta proteins, become rogue and kill healthy nerve cells.
“While the amyloid hypothesis is a prevalent view, it has not been fully validated in part because amyloid-beta oligomers are so difficult to detect, so there are differing opinions on what causes Alzheimer’s disease,” said Prof Vendruscolo.
“The discovery of an antibody to accurately target oligomers is, therefore, an important step to monitor the progression of the disease, identify its cause, and eventually keep it under control.”
The inability to detect oligomers has been a major obstacle in the progress of Alzheimer’s research, hampering the development of effective diagnostic and therapeutic interventions.
The new method is based on an approach for antibody discovery developed over the last ten years at the Centre for Misfolding Diseases, enabling the design of antibodies for challenging antigens, including those that live for a very short time.
The researchers used a design strategy to target the epitopes of the oligomers in vitro and in vivo experiments to create an antibody with at least three orders of magnitude greater affinity for the oligomers over other forms of amyloid-beta.
This, say the research team, is the key feature that enables the antibody to specifically quantify oligomers in both in vitro and in vivo samples.
Study first author Dr Francesco Aprile said: “Our method allows the generation of antibody molecules able to target oligomers despite their heterogeneity, and we hope it could be a significant step towards new diagnostic approaches.”
PNAS 25 May 20202
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