Researchers at the Max Delbrück Center for Molecular Medicine in Berlin, have discovered elevated levels of a protein known as Arl8b in Alzheimer’s disease brain models, marking it as a potential target for treatment of the condition.
The most widely known biomarkers for Alzheimer’s disease are amyloid beta plaques and tau tangles—proteins accumulating in the brain due to genetic mutations leading to the buildup of aggregates and eventually neuronal cell death. While treatments for these targets already exist, their effectiveness in slowing cognitive decline varies. As a result, scientists are actively searching for new markers of the disease.
Reporting in Genome Medicine, researchers have now investigated changes in the proteome of Alzheimer’s disease patients extending beyond the known markers in order to understand the interplay between all proteins involved in the onset of the disease.
“We’re lacking good diagnostic markers that would allow us to reliably detect the disease at an early stage or make predictions about its course,” explained Professor Erich Wanker, head of the Proteomics and Molecular Mechanisms of Neurodegenerative Diseases Lab at the Max Delbrück Center and senior author of the study.
For their study, the scientists genetically modified mice to express five mutations associated with familial Alzheimer’s disease including the presence of amyloid beta plaques and dementia. Protein changes in the mice brains and brain samples from Alzheimer’s patients were then analyzed using a technique known as immunohistochemistry and compared to healthy controls.
“During our analyses, we noticed that a protein called Arl8b was building up in mouse brains, along with the amyloid-beta plaques,“ said Annett Böddrich, academic researcher at the Max Delbrück Center for Molecular Medicine and lead author of the paper, in a press statement.
The ArI8b protein has been previously associated with cell organelles known as lysosomes —responsible for the degradation of excess or worn-out cell parts including protein aggregates. According to the scientists, Alzheimer’s patients showed significantly higher levels of Arl8b in cerebrospinal fluid tests compared to control samples.
Because cerebrospinal fluid is more easily accessible than brain tissues for Alzheimer’s disease diagnostics, presence of Arl8b in the fluid marks it as a potential diagnostic marker for the condition. However, despite the hopeful results the scientists acknowledge that only a small group of Alzheimer’s patients were considered and that more research will be needed to confirm the findings.
“It’s too early to hope for a diagnostic test,” said Wanker. Nevertheless, he remains optimistic: “Our work shows that proteomic research can provide crucial information for identifying disease mechanisms and markers, and thereby move research forward. Also, this doesn’t just apply to Alzheimer’s; it’s also relevant to other complex neurodegenerative diseases such as Parkinson’s and Huntington’s.”
