Alzheimer’s may trick the brain into erasing its own memories

 Alzheimer's disease is known for one devastating effect above all others. It steadily destroys brain cells and the connections between them, breaking down the neural networks that allow us to store and recall memories.

What remains far less certain is how this destruction begins. One leading explanation focuses on amyloid beta, a protein fragment that can accumulate in the brain and harm neurons. But scientists have also linked Alzheimer's to many other factors, including tau proteins, lysosomes, chronic inflammation, immune cells called microglia, and additional biological processes.A Possible Link Between Two Major Theories

Researchers now believe they may have found a way to connect two of the most prominent ideas about how Alzheimer's develops. In a study published in Proceedings of the National Academy of Sciences, scientists report new evidence that amyloid beta and inflammation may act through the same molecular pathway. Both appear to converge on a specific receptor that signals neurons when to eliminate synapses, the contact points that allow brain cells to communicate.

The research was led by Wu Tsai Neurosciences Institute affiliate Carla Shatz, the Sapp Family Provostial Professor, along with first author Barbara Brott, a research scientist in Shatz's laboratory. The work received partial support from a Catalyst Award from the Knight Initiative for Brain Resilience, a program focused on reexamining the basic biology behind neurodegenerative diseases such as Alzheimer's.

The Role of a Synapse Pruning Receptor

One major component of the study builds on earlier work involving a receptor known as LilrB2. Shatz has studied this molecule for years. In 2006, she and her colleagues discovered that the mouse version of LilrB2 plays an essential role in synaptic pruning, a normal process during brain development and learning in adulthood.

Later findings connected this same receptor to Alzheimer's. In 2013, Shatz's team showed that amyloid beta can bind to LilrB2. When this happens, neurons are triggered to remove synapses. Importantly, experiments also showed that removing the receptor genetically protected mice from memory loss in an Alzheimer's disease model.

Inflammation and the Complement Cascade

The second major line of research examined an immune process known as the complement cascade. Under healthy conditions, this system releases molecules that help the body eliminate viruses, bacteria, and damaged cells.

Source: ScienceDaily