Transplantation of new brain cells reverses memory loss in Alzheimer's disease model

July 16, 2014
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

A new study from the Gladstone Institutes has revealed a way to alleviate the learning and memory deficits caused by apoE4, the most important genetic risk factor for Alzheimer's disease, improving cognition to normal levels in aged mice.

In the study, which was conducted in collaboration with researchers at UC San Francisco and published today in the Journal of Neuroscience, scientists transplanted inhibitory neuron progenitors—early-stage brain cells that have the capacity to develop into mature —into two mouse models of Alzheimer's disease, apoE4 or apoE4 with accumulation of amyloid beta, another major contributor to Alzheimer's. The transplants helped to replenish the brain by replacing cells lost due to apoE4, regulating brain activity and improving learning and memory abilities.

"This is the first time transplantation of inhibitory neuron progenitors has been used in aged Alzheimer's disease models," said first author Leslie Tong, a graduate student at the Gladstone Institutes and UCSF. "Working with older animals can be challenging from a technical standpoint, and it was amazing to see that the cells not only survived but affected activity and behavior."

The success of the treatment in older mice, which corresponded to late adulthood in humans, is particularly important, as this would be the age that would be targeted were this method ever to be used therapeutically in people.

"This is a very important proof of concept study," said senior author Yadong Huang, MD, PhD, an associate investigator at Gladstone Institutes and associate professor of neurology and pathology at UCSF. "The fact that we see a functional integration of these cells into the hippocampal circuitry and a complete rescue of learning and in an aged model of Alzheimer's disease is very exciting."

A balance of excitatory and inhibitory activity in the brain is essential for normal function. However, in the apoE4 model of Alzheimer's disease—a that is carried by approximately 25% of the population and is involved in 60-75% of all Alzheimer's cases—this balance gets disrupted due to a decline in inhibitory regulator cells that are essential in maintaining normal brain activity. The hippocampus, an important memory center in the brain, is particularly affected by this loss of inhibitory neurons, resulting in an increase in network activation that is thought to contribute to the learning and memory deficits characteristic of Alzheimer's disease. The accumulation of amyloid beta in the brain has also been linked to this imbalance between excitatory and inhibitory activity in the brain.

In the current study, the researchers hoped that by grafting inhibitory neuron progenitors into the hippocampus of aged apoE4 mice, they would be able to combat these effects, replacing the lost cells and restoring normal function to the area. Remarkably, these new inhibitory neurons survived in the hippocampus, enhancing inhibitory signaling and rescuing impairments in learning and memory.

In addition, when these inhibitory progenitor cells were transplanted into apoE4 mice with an accumulation of amyloid beta, prior deficits were alleviated. However, the new inhibitory neurons did not affect levels, suggesting that the cognitive enhancement did not occur as a result of amyloid clearance, and amyloid did not impair the integration of the transplant.

According to Dr. Huang, the potential implications for these findings extend beyond the current methods used. "Stem cell therapy in humans is still a long way off. However, this study tells us that if there is any way we can enhance inhibitory neuron function in the hippocampus, like through the development of small molecule compounds, it may be beneficial for Alzheimer disease patients."

Explore further: Rescue of Alzheimer's memory deficit achieved by reducing 'excessive inhibition'

Related Stories

Rescue of Alzheimer's memory deficit achieved by reducing 'excessive inhibition'

June 13, 2014
A new drug target to fight Alzheimer's disease has been discovered by a research team led by Gong Chen, a Professor of Biology and the Verne M. Willaman Chair in Life Sciences at Penn State University. The discovery also ...

Compound reverses symptoms of Alzheimer's disease in mice, research shows

May 20, 2014
A molecular compound developed by Saint Louis University scientists restored learning, memory and appropriate behavior in a mouse model of Alzheimer's disease, according to findings in the May issue of the Journal of Alzheimer's ...

Blame it on the astrocytes

July 11, 2014
In the brains of all vertebrates, information is transmitted through synapses, a mechanism that allows an electric or chemical signal to be passed from one brain cell to another. Chemical synapses, which are the most abundant ...

Low doses of antianxiety drugs rebalance the autistic brain

March 19, 2014
New research in mice suggests that autism is characterized by reduced activity of inhibitory neurons and increased activity of excitatory neurons in the brain, but balance can be restored with low doses of a well-known class ...

Modified stem cells offer potential pathway to treat Alzheimer's disease

April 15, 2014
UC Irvine neurobiologists have found that genetically modified neural stem cells show positive results when transplanted into the brains of mice with the symptoms and pathology of Alzheimer's disease. The pre-clinical trial ...

Recommended for you

Study shows video games could cut dementia risk in seniors

November 16, 2017
Could playing video games help keep the brain agile as we age?

New player in Alzheimer's disease pathogenesis identified

November 14, 2017
Scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) have shown that a protein called membralin is critical for keeping Alzheimer's disease pathology in check. The study, published in Nature Communications, ...

Biomarker may predict early Alzheimer's disease

November 10, 2017
Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a peptide that could lead to the early detection of Alzheimer's disease (AD). The discovery, published in Nature Communications, may ...

Smell test challenge suggests clinical benefit for some before development of Alzheimer's

November 10, 2017
Researchers at Columbia University Medical Center (CUMC) and the New York State Psychiatric Institute (NYSPI) may have discovered a way to use a patient's sense of smell to treat Alzheimer's disease before it ever develops. ...

How SORLA protects against Alzheimer's disease

November 7, 2017
Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a new protective function for a brain protein genetically linked to Alzheimer's. The findings, published in the Journal of Experimental ...

Saving neurons may offer new approach for treating Alzheimer's disease

November 6, 2017
Treatment with a neuroprotective compound that saves brain cells from dying also prevents the development of depression-like behavior and the later onset of memory and learning problems in a rat model of Alzheimer's disease. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.