Why a cerebral circuit collapses first in Alzheimer’s disease

Virginia Tech scientists have investigated how mitochondrial stress and calcium overload can cause Alzheimer’s To strike the memory circuits first, offering indices on the first breakdown of the disease.

One of the first parts of the brain affected by Alzheimer’s disease is the Entorhinal Cortex – a region that plays a large role in memory, spatial navigation and the internal brain cartography system.

With the support of the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund (Ardraf), the Fratin Biomedical Research Institute of VTC Scientists Sharon Sanger and Shannon Farris are working to understand why this field is particularly vulnerable.

Bridging synapses and mitochondria

Swanger studies how brain cells communicate through synapses in cerebral circuits sensitive to the disease, while Farris focuses on how different circuits in the brain memory center work at the molecular level. Their overlapping expertise has made the collaboration a natural adjustment.

“We have both studied the difficulty of circuits at the molecular level for some time,” said Swanger, assistant professor at the Research Institute. “This new collaborative project brings together my work on synapses and Shannon on mitochondria in a way that fills a big gap in the field of Alzheimer’s disease.”

“This type of state support is essential,” said Farris. “This gives researchers in Virginia the possibility of asking questions that could possibly make a difference for people living with Alzheimer’s disease. It is significant to be part of the research that could help people face this trip. ”

Mitochondria under stress

A key objective of their research is the mitochondria – of tiny structures within the brain cells which provide the energy necessary for a variety of cellular functions in neurons, including synaptic transmission. In Alzheimer’s disease, mitochondria cease to work properly during the disease.

Farris and Swanger are studying if mitochondria in a vulnerable circuit linked to memory can become overloaded with calcium, a key signaling product for several neural and synaptic processes. This overload could contribute to the early ventilation of memory circuits.

Watch the connections fail

“The link between these cells is one of the first to fail in Alzheimer’s disease,” said Farris. “We found it synapse To unusually solid calcium signals in neighboring mitochondria – so strong that we can see them clearly under the optical microscope. These types of signals are difficult to ignore. It gives us a model where we can really look at what’s going on while things are starting to go wrong. »»

To test their hypothesis, researchers will study the brain tissues of healthy mice and mice with certain aspects of Alzheimer’s pathology. By comparing the functioning of mitochondria and how brain cells communicate through the synapses in each group, they hope to find early signs of stress or failure in the Cortex circuit and the Entorhinal Hippocampus.

Swanger and Farris are members of the Research Center for Neurobiology of the Biomedical Research Institute Fratin and also professors from the Department of Biomedical Sciences and Pathobiology of Virginia-Maryland College of Veterinary Medicine.

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