A potential new biomarker for Alzheimer’s

Alzheimer’s is considered a disease of old age, with most people being diagnosed after the age of 65. However, the condition actually begins to progress unnoticed years before symptoms appear. Small proteins, known as amyloid-beta peptides, clump together in the brain to form plaques. This plaque causes inflammation and eventually leads to nerve cell death.

Protein interactions in the brain reveal disease mechanisms

What triggers these pathological changes is still unclear. “We lack good diagnostic markers that will allow us to reliably detect the disease at its early stages or make predictions about its course,” says Professor Erich Wanker, head of the Laboratory of Proteomics and Molecular Mechanisms of Neurodegenerative Diseases at the Max Delbrück Center. Wanker and his team are studying the brains of people with Alzheimer’s disease to understand their proteome – the interactions between all the proteins involved in the onset and course of the disease. Write on Genome Medicine, the researchers now report a new actor in the pathological process. Their discoveries will help scientists understand the mechanisms underlying Alzheimer’s and may also serve as markers for better diagnosis.

To analyze changes in the proteome, Wanker’s team studied genetically modified mice. The mice have five mutations that occur in people with familial Alzheimer’s disease. Amyloid-beta plaques develop in the brains of mice and the animals show characteristic symptoms, such as dementia.

New perspectives for a better understanding of Alzheimer’s

“During our analysis, we noticed that a protein called Arl8b accumulates in the mouse brain, along with amyloid-beta plaques,” said Annett Böddrich, lead author of the paper. The researchers also found protein accumulation in brain samples from Alzheimer’s patients.

Arl8b is associated with lysosomes, cell organelles involved in the decomposition of protein clumps. A different research team recently made an interesting discovery in nematode worms: increased Arl8b production can decrease plaque, which reduces nerve cell damage. Closer study of Arl8b could hold the key to better understanding Alzheimer’s disease – and could provide new targets for therapy.

Interesting candidate for a diagnostic marker

But there’s more: “We were able to show that Alzheimer’s patients have significantly more Arl8b in their cerebrospinal fluid than healthy controls,” says Böddrich. Unlike brain tissue, cerebrospinal fluid is easily accessible for diagnostic studies. “This means Arl8b is an attractive candidate for a diagnostic marker,” he said.

However, this study only looked at a small group of Alzheimer’s patients, so expectations should be kept under control: “It is too early to expect diagnostic tests,” says Wanker. Nevertheless, he is optimistic: “Our work shows that proteomics research can provide important information for identifying disease mechanisms and markers, and thereby advancing research. Also, this doesn’t just apply to Alzheimer’s; it is also relevant to other complex neurodegenerative diseases such as Parkinson’s and Huntington’s.

Further information

How Misfolded proteins harm our brains

Wrong folding in the Alzheimer’s brain

Wankers laboratory

Max Delbrueck Center

The Max Delbrück Center for Molecular Medicine at the Helmholtz Association (Max Delbrück Center) is one of the world’s leading biomedical research institutions. Max Delbrück, a native of Berlin, is a Nobel laureate and one of the founders of molecular biology. At sites in Berlin-Buch and Mitte, researchers from around 70 countries study human biology – investigating the foundations of life from the most basic building blocks to the mechanics of entire systems. By understanding what regulates or disrupts the dynamic balance of cells, organs or the whole body, we can prevent disease, diagnose it early and halt its progression with tailored therapy. Patients should benefit as soon as possible from basic research findings. Therefore, the Max Delbrück Center supports the creation of spin-offs and participates in collaborative networks. It works in close partnership with Charité – Universitätsmedizin Berlin in the co-managed Center for Experimental and Clinical Research (ECRC), the Berlin Institute of Health (BIH) in Charité, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the Max Delbrück Center currently employs 1,800 people and is funded 90 percent by the German federal government and 10 percent by the State of Berlin.