- A research team
from Columbia University Medical Centre has found that accumulation of tau
protein in grid cells leads to cognitive decline among Alzheimer's
- The reduction in
spatial cognition could lead to wandering among Alzheimer's patients
- This could lead
to a potential new target for diagnosing and developing drug therapy for
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
provide a new target for the treatment of a very troubling symptom, that of
wandering, among the patients.
‘The identification of Tau pathology could control wandering in Alzheimer’s patients and may provide a new target for diagnosing and developing drugs for the disease.’
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
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
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.
The study found that
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.
- Among mice which
expressed tau, special cognitive tasks were performed worse than normal
- 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
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
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."
The study findings
suggest possible methods of treatment that include
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
People with memory
problems, even early stages of dementia, are at risk of becoming disoriented
- 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.
- 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
- Wandering and Getting Lost - (http://www.alz.org/care/alzheimers-dementia-wandering.asp)