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What is the mechanism in the brain by which memory loss occurs in Alzheimer’s?
Sara Calafate
VIB-KU Leuven Center for Brain and Research Disease
Gent, Belgium
Background
Memories are usually formed when two critical regions in the brain- the entorhinal cortex and hippocampus - communicate with each other through electrical signals. In the early stages of Alzheimer’s individuals experience mild memory loss and confusion. However, the memory loss progresses as the disease advances - such as unable to recognize family members, forgetting relationships, forgetting purpose of common items such as a pen or fork etc. The main underlying cause of this memory loss and confusion is the progressive damage to brain cells caused by Alzheimer’s and the exact mechanism is not well understood.
Past studies suggest that in Alzheimer’s, the nerve cells in these two regions are damaged and are unable to “talk” to each other leading to memory defects. Scientists are trying to understand the specific biological processes affected by Alzheimer’s, which result in disrupting memory. Dr. Sara Cesariny Calafate proposes to identify when and why during Alzheimer’s does communication stop between the two brain regions and investigate the precise cause of such changes.
Research Plan
Dr. Calafate and her team will study the molecular changes that take place between the two brain regions in the early stages of Alzheimer’s using genetically engineered Alzheimer’s-like mouse models. Past studies have reported that during early stage of Alzheimer’s, a region within the hippocampus exhibits excessive activity, due to accumulation of beta-amyloid plaques- a hallmark of Alzheimer’s. Dr. Calafate plans to investigate the role of plaques in impacting the communication between the two brain regions and what molecular changes govern this process. This could throw light on mechanism underlying the nerve cell network dysfunction between the two brain regions. The researchers plan to perform experiments to analyze the ability of affected nerve cells in a region within the hippocampus to generate and propagate electrical signals, which could throw light on how the network dysfunctions.
When the tau protein gets misfolded and forms masses or aggregates, it gives rise to tau tangles - another hallmark of Alzheimer’s. Dr. Calafate plans to inject tau tangles from the human brain into the brain of Alzheimer’s-like mice to observe how these toxic effects interfere with the cross-talk between the two brain regions. Using molecular biology techniques that follow which genes are either turned on or off in single affected nerve cells the researchers hope to identify biochemical changes that disrupt the brain network circuitry leading to cognitive impairment.
Impact
The results of this project will shed new light in revealing nerve cell property changes in the early onset of Alzheimer’s. They could also pave the way for designing new therapies to stabilize network activity in brain regions that preserve memory.
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