Amyloid formation drives brain tissue loss in animal studies

New findings show that the formation of amyloid plaques drives damage and tissue loss in the brain during Alzheimer’s disease in animals, but lithium reduces the life-shortening effects of this loss.

Amyloid plaque formation directly causes brain tissue loss in animals, but a drug called lithium reduces the life-shortening effects of this loss, shows a study published today in eLife.

Patients with Alzheimer’s disease experience progressive memory loss and loss of brain matter over time. This study provides new details about what happens in the brain in Alzheimer’s disease and suggests a potential strategy to slow it.

Both the production of small protein fragments called Amyloid-ß and the assembly of these fragments into large clusters or plaques have been implicated in Alzheimer’s disease. But teasing apart the role of Amyloid-ß versus the role of plaque formation has been difficult.

“There is currently a lack of tools that can directly control the formation of Amyloid-ß plaques in animals, which would allow scientists to examine the effects of plaque formation in Alzheimer’s disease,” explains lead author Lim Chu Hsien, a researcher at and recent graduate of Yale-NUS College, Singapore, who is currently pursuing her medical degree at Duke-NUS Medical School, Singapore.

Using a technique called optogenetics, Lim and her colleagues were able to engineer Amyloid-ß fragments that would form plaques when exposed to light in the brains of fruit flies, tiny worms and zebrafish. The experiments showed that both the presence of Amyloid-ß and the formation of plaques were detrimental to the lifespan and health of these animals.

The team found that formation of the plaques caused both metabolic problems in the brain and physical damage that led to a loss of brain tissue. It also impaired the animals’ sensory motor skills and behaviour.

Next, the researchers tested whether a drug called lithium that is used to treat some psychiatric disorders might mitigate the harm caused by light-induced plaque formation in fruit flies. They added lithium to the flies’ food and found that this led to an extended lifespan in the insects.

“These data demonstrate the potential use of our optogenetics system for Alzheimer’s disease drug testing,” explains senior author Nicholas Tolwinski, Associate Professor of Science (Life Sciences) at Yale-NUS College, Singapore. “This light-driven plaque formation approach could be used in cells to enable mass screening of potential treatments. It might also help scientists study the effects of treatments on the different stages of Alzheimer’s disease development.”

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Reference

The paper ‘Application of optogenetic Amyloid-ß distinguishes between metabolic and physical damage in neurodegeneration’ can be freely accessed online at https://doi.org/10.7554/eLife.52589. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

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About eLife

eLife is a non-profit organisation inspired by research funders and led by scientists. Our mission is to help scientists accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours in science. We publish important research in all areas of the life and biomedical sciences, including Developmental Biology and Neuroscience, which is selected and evaluated by working scientists and made freely available online without delay. eLife also invests in innovation through open-source tool development to accelerate research communication and discovery. Our work is guided by the communities we serve. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, the Wellcome Trust and the Knut and Alice Wallenberg Foundation. Learn more at https://elifesciences.org/about.

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About Yale-NUS College

Established in 2011, through a partnership between Yale University and the National University of Singapore, Yale-NUS College is a leading liberal arts and sciences college in Asia, with a full residential programme that integrates living and learning. Drawing on the resources and traditions of its two founding universities, a Yale-NUS College education promotes broad-based interdisciplinary learning across the natural sciences, social sciences and humanities complemented by depth of expertise in one’s major. Our curriculum and pedagogy draws on the strengths of established traditions in the liberal arts and sciences, while introducing our students to the diverse intellectual traditions and cultures of Asia and the world. We nurture young minds and equip the next generation with the means to appreciate and understand complex issues, the capacity to think critically and problem solve, and the skills to communicate effectively and lead. 

Published: 31 Mar 2020

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