Sign In
International
News release
From:
In Alzheimer's, excess tau protein damages brain's GPS
Dr. Duff and her colleagues focused their investigations on excitatory grid cells, a type of nerve cell in the EC that fires in response to movement through space, creating a grid-like internal map of a person's environment. The researchers made electrophysiological recordings of the grid cells of older mice--including mice engineered to express tau in the EC (EC-tau mice) and normal controls--as they navigated different environments. Spatial cognitive tasks revealed that the EC-tau mice performed significantly worse compared to the controls, suggesting that tau alters grid cell function and contributes to spatial learning and memory deficits, according to co-study leader Abid Hussaini, PhD, assistant professor of neurobiology (in Pathology and Cell Biology and the Taub Institute).
Detailed histopathological analysis of the mouse brains revealed that only the excitatory cells, but not the inhibitory cells, were killed or compromised by pathological tau, which probably resulted in the grid cells firing less. "It appears that tau pathology spared the inhibitory cells, disturbing the balance between excitatory and inhibitory cells and misaligning the animals' grid fields," said co-first author Hongjun Fu, PhD, associate research scientist in the Taub Institute, who led the immunohistological and behavior studies.
"This study clearly shows that tau pathology, beginning in the entorhinal cortex, can lead to deficits in grid cell firing and underlies the deterioration of spatial cognition that we see in human Alzheimer's disease," said Eric Kandel, MD, Nobel laureate, University Professor and Kavli Professor of Brain Science at CUMC. "This is a classic advance in our understanding of the early stages of Alzheimer's disease."
"This study is the first to show a link between grid cells and Alzheimer's disease," said Edvard E. Moser, Nobel laureate and head of the Kavli Institute for Systems Neuroscience at Norwegian University of Science and Technology. "These findings will be crucial for future attempts to understand the development of early Alzheimer's disease symptoms, including the tendency to wander and get lost."
The findings raise the possibility that spatial disorientation could be treated by correcting this imbalance through transcranial stimulation, deep-brain stimulation, or light-based therapy.
"We have a lot to learn about grid cells and how they are affected by Alzheimer's disease," said Gustavo A. Rodriguez, PhD, a postdoctoral research scientist in the Taub Institute and a co-author of the paper. "We don't yet know what percentage of healthy grid cells are needed for proper navigation or whether this system is rescuable once it has been compromised."
"In the meantime," said Dr. Duff, "our findings suggest that it may be possible to develop navigation-based cognitive tests for diagnosing Alzheimer's disease in its initial stages. And if we can diagnose the disease early, we can start to give therapeutics earlier, when they may have a greater impact."
Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Dr Bryce Vissel is a Professor in the School of Clinical Medicine at UNSW and Director of the Centre for Neuroscience and Regenerative Medicine at St Vincent's Hospital Sydney
The study led by Professor Karen Duff from Columbia University and colleague Abid Hussaini is excellent science that has significant implications for our understanding of Alzheimer’s disease. Disorientation is a common feature in Alzhiemer's patients that leads to many patients wandering. It is not uncommon to hear of situations where patients find themselves lost, disoriented and confused and consequently distressed as the disease progresses. This also leads to great distress for the families. The brain of Alzheimer’s patients is characterised by the presence of plaques and tangles. Plaques are made of a molecule called amyloid and tangles are made up of a substance called tau. While many investigators have focused on amyloid, others are beginning to look at ‘tau’ in order to understand its role in causing the disease. In this study, led by Professors Duff and Hussaini, the investigators looked at how tau can damage the brain and how it may contribute to the dreadful memory loss that is characteristic of Alzheimer’s disease, early in the disease. Remarkably, they showed that cells, called ‘grid cells’ that are known to be involved in navigation were among the earliest to be damaged in a mouse model of Alzheimer’s disease. This study is the first to show a link between grid cells and Alzheimer's disease and to implicate tau in the damage to those cells. These findings are incredibly interesting and important for understanding the development of Alzheimer's disease symptoms, especially the tendency to wander and get lost. Most importantly, fundamental understandings like this provide an insight into the disease that ultimately lead to new cognitive and other therapeutic strategies.
Science is crucial for solving diseases like Alzheimer’s, for which there is currently no cure - and it is urgent that cures are found. There are more than 353,800 Australians living with dementia and 46.8 million worldwide. Without a medical breakthrough, the number of people with dementia in Australia is expected to be almost 900,000 by 2050. It is also increasingly urgent that scientists investigate a range of new approaches to solving this disease.
Attachments
Note: Not all attachments are visible to the general public. Research URLs will go live after the embargo ends.
