Tau Protein Damages the Brain in Alzheimer’s Patients and Could Make Them Wander

The spatial disorientation which results in wandering of many Alzheimer's disease, may be due to the accumulation of tau protein in the navigational nerve cells of the brain, finds a study from the Columbia University Medical Center (CUMC). The study published in the journal Neuron could aid in early detection of Alzheimer’s disease and could provide a new target for the treatment of a very troubling symptom, that of wandering, among the patients.

Alzheimer’s Patients’ Wander

One of the major concerns regarding Alzheimer’s is that three out of five people wander and are unable to find their way back. This behavior is generally identified during the early stages of the disease and increases the risk of injury.

The problems are suspected to originate in the entorhinal cortex of the brain and this region is associated with memory and navigation. This region of the brain is the primary brain structure which contains a large amount of tau protein and is associated with a build-up of neurofibrillary tangles.

Dr. Karen Duff who is a professor of pathology and a co-study leader said that no one has been able to show until now how the increase in tau may affect the ability of the patients to navigate.

Experiments on Excitatory Grid Cell

The research team lead by Dr. Duff worked on understanding the excitatory grid cells, which are a type of nerve cells in the entorhinal cortex that provides a response to movement through space. This results in a grid-like map of the environment of the person.

 The study involved electrophysiological recordings of the grid cells in mice that were genetically altered to express tau in the entorhinal cortex as well as in normal mice. The mice were made to move around in the environment.

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The study found that

• Among mice which expressed tau, special cognitive tasks were performed worse than normal mice.
• This suggested that tau protein affects the functions of the grid cells
• The significance of the grid cells in spatial learning as well as in memory was identified.
• On performing a detailed histopathology of the mouse brains, it was found that the excitatory cells were killed or lowered in efficiency due to tau, without any effect on the inhibitory cells. Dr. Hongjun who is an associate research scientist in the Taub Institute, said, "It appears that Tau pathology spared the inhibitory cells, disturbing the balance between excitatory and inhibitory cells and misaligning the animals' grid fields."

The study aided in highlighting the importance of Tau pathology, which begins in the entorhinal cortex and results in the deficits in the grid cell firing. It plays an important role in the deterioration of the spatial cognition that is one of the hallmark symptoms of Alzheimer’s disease. The understanding obtained about Tau pathology from this study can be used to develop therapeutic methods that prevent the increase in tau, thereby lowering the risk of cognitive decline.

First Study to Show Link Between Grid Cells and Alzheimer’s Disease

Nobel Laureate, Dr. Edvard E. Moser who is the Head of the Kavli Institute for Systems Neuroscience, said, "This study is the first to show a link between grid cells and Alzheimer's disease. 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."

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The study findings suggest possible methods of treatment that include

• Deep-brain stimulation
• Light-based therapy
• Transcranial stimulation

The research team says that further studies need to be conducted on the effect of tau in the cells to understand what percentage of the healthy cells are required to maintain the ability to navigate among Alzheimer patients. Moreover, more details are required to identify if the grid cells are rescuable.

Dr. Duff stated, "In the meantime, 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."

6 out of 10 People with Alzheimer’s Wander

A person suffering from Alzheimer's disease may become disoriented, forget names and address even in places that were familiar. Though this can be dangerous, there are strategies that are required to prevent it.

People at Risk of Wandering

People with memory problems, even early stages of dementia, are at risk of becoming disoriented and confused.

• Talks about going home when at home
• Returns from a walk much later than usual
• Tries to complete tasks that were over a long time ago
• Seems restless
• Asks about friends past friends or family and their whereabouts

The risk of wandering is considerable but the family and friends need to stay vigilant to keep the patients safe. The current study that focuses on the damage caused due to the accumulation of tau in the grid cells will aid in drug therapy that will lower the risk of this dreaded symptom.

References:

1. Karen E. Duff et al. Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease. Neuron, January (2017) DOI: 10.1016/j.neuron.2016.12.023
2. Wandering and Getting Lost - (http://www.alz.org/care/alzheimers-dementia-wandering.asp)

Source-Medindia