Sixty percent of Alzheimer's patients wander and get lost. This can lead to injury, harm and even death.
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It is important to note that 60 percent of Alzheimer's patients are likely to wander. One of the things that always surprises me an Alzheimer's patients wanders and is eventually found is what their family and caregivers say - they never wandered before.
This has happened to readers of the Alzheimer's Reading Room. Like this one.
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Columbia University Medical Center (CUMC) researchers have discovered that the spatial disorientation that leads to wandering in many Alzheimer's disease patients is caused by the accumulation of tau protein in navigational nerve cells in the brain.An estimated three out of five people with Alzheimer's disease wander and get lost, usually beginning in the early stages of the disease, leaving them vulnerable to injury.
- Researchers suspect that these problems originate in an area of the brain known as the entorhinal cortex (EC).
- The EC plays a key role in memory and navigation and is among the first brain structures affected by the buildup of neurofibrillary tangles that are largely composed of tau, a hallmark of Alzheimer’s disease.
“Until now, no one has been able to show how tau pathology might lead to navigational difficulties,” said co-study leader Karen E. Duff, PhD, professor of pathology & cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at CUMC.
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.
- Detailed 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.
“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. 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.
“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.”
The study was published online in the journal Neuron.
The findings, in mice, could lead to early diagnostic tests for Alzheimer's and highlight novel targets for treating this common and troubling symptom.
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“Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease.”
The study was supported by grants from National Institutes of Health (R01NS074874 and R01AG050425) and the Alzheimer’s Association (2015-NIRG-341570).
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The authors declare no financial or other conflicts of interest.
Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. For more information, visit cumc.columbia.edu or columbiadoctors.org.
The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center and New York-Presbyterian Hospital brings together researchers and clinicians across disciplines to uncover the causes of Alzheimer’s, Parkinson’s, and other age-related brain diseases, and to discover ways to treat, prevent, and ultimately cure these diseases. For more information, visit The Taub Institute at http://www.cumc.columbia.edu/dept/taub/.