Mount Sinai Study Maps Protein Networks Driving Pathogenesis of Alzheimer’s Disease

A new study led by ICAHN School of Medicine on Mount Sinai offers one of the most comprehensive views on how brain cells interact with Alzheimer’s disease, mapping networks of protein that reveal communication failures and show new therapeutic opportunities.

Published on the Internet at Cell On September 25, the study analyzed the effect of protein on the brain tissue by almost 200 people. Researchers have found that disorders in communication between neurons and supporting brain cells called glia-especially astrocytes and microgly-are closely associated with the progression of Alzheimer’s disease. A protein in particular, called AHNAK, was recognized as a leading guide to these harmful interactions.

Alzheimer is not just about the accumulation of plaque or dying neurons. This is how the whole brain ecosystem collapses. Our study shows that the loss of hygiene communication between neurons and global cells can be a major cause of the disease. ”

Bin Zhang, PhD, Senior writer, Willard TC Johnson Research Professor of Neurogenetics and Director of the Center for Transforming Modeling Disease at ICAHN Medical School

Most Alzheimer’s surveys focused on the accumulation of amyloid and Tau plates. But these accumulation of proteins do not explain the full history and some treatments aimed at plates only give a moderate benefit. In this study, the group took what is known as a “non-monitoring” approach-a analysis that does not start with cases of proteins that are more important than examining the brain tissue samples of about 200 people with and without Alzheimer’s disease.

“This study took a broader view, examining how more than 12,000 proteins interact within the brain,” said co-symbatriotis Junmin Peng, a doctorate, member and professor of structural biology and developmental neurobiology at St. Jude. “Using protein profile profile technology, we quantified the expression of protein throughout the brain, allowing a comprehensive view of protein -like changes and interactions in Alzheimer’s.”

Using advanced computational modeling, they built large -scale networks that mapped how these proteins interact and were identified where communication breaks into illness, allowing the identification of whole systems that go wrong, instead of focusing on a single molecule. The most critical of these systems is Glia-Neuron communication, which is right in the center of Alzheimer’s protein networks. In healthy brains, the neurons send and receive signals, while glia cells support and protect them. But in Alzheimer’s, this balance seems to be lost: Glois cells become overactive, neurons become less functional and inflammation increases. This change was consistent in many independent data sets.

By analyzing how the protein networks shifted to Alzheimer’s, the researchers recognized a number of basic-molecs-molecules proteins that seem to play overcrowded roles in activating or accelerating the disease.

Ahnak, a protein found mainly in astrocytes, was one of the top drivers. The group found that AHNAK levels are increasing as Alzheimer’s progresses and is associated with higher levels of toxic proteins in the brain, such as amyloid beta and Tau. To test their effects, they used models of human brain that come from stem cells. The decrease in AHNAK in these cells has led to a fall in TAU levels and improved neurons function when co-cultivated in the laboratory.

“These results indicate that Ahnak could be a very promising therapeutic goal,” said co-symbatriotis Dongming Cai, MD, PhD, Professor of Neurology and Director of the Grossman Research and Memory Center at the University of Mines. “By reducing its activity, we have seen both less toxicity and more neuronal activity, two encouraging signs that we may be able to restore healthier brain function.”

While AHNAK is a powerful candidate for future drug development, research also provides a wider context for Alzheimer’s understanding and treatment. The study has identified more than 300 proteins that have rarely been studied in the disease, offering new research directions.

He also showed that different biological factors, such as gender and genetic background, can affect the way these protein networks are behaving. For example, people with the APOE4 Gene, a well -known genetic risk factor for Alzheimer’s, showed separate network disorder standards compared to those without the gene.

While more work is needed to study AHNAK and other basic proteins in live systems, integrated data from this study is available to the public to researchers worldwide, accelerating progress throughout the field.

“This study opens a new way of thinking about Alzheimer’s, not only as an accumulation of toxic proteins, but as a breakdown in the way in which brain cells speak to each other,” Dr. Zhang added. “By understanding these conversations and where they go wrong, we can begin to develop treatments that bring the system back into balance.”