(Press-News.org) SAN FRANCISCO, CA—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 inhibitory neurons—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 memory deficits 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 genetic risk factor 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 amyloid beta 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."
INFORMATION:
Other scientists who participated in this research include Biljana Djukic, Anna Gillespie, Seo Yeon Yoon, Max Wang, Olivia Zhang, and Johanna Knoferle from Gladstone Institutes, and Christine Arnold, John Rubenstein, and Arturo Alvarez-Buylla from UCSF. Funding was provided by the California Institute for Regenerative Medicine, National Institutes of Health, S.D. Bechtel, Jr. Foundation, Roddenberry Foundation, and Hellman Foundation.
About the Gladstone Institutes
To ensure our work does the greatest good, the Gladstone Institutes focus on conditions with profound medical, social, and economic impact – unsolved diseases of the heart, the brain, and the immune system. Gladstone is affiliated with the University of California, San Francisco, and it is an independent, nonprofit biomedical research organization using visionary science and technology to overcome diseases and enrich society.
Transplantation of new brain cells reverses memory loss in Alzheimer's disease model
2014-07-16
ELSE PRESS RELEASES FROM THIS DATE:
JAMA study: Stroke risk and death rates fall over past 2 decades
2014-07-15
Fewer Americans are having strokes and those who do have a lower risk of dying from them finds a new study led by Johns Hopkins Bloomberg School of Public Health researchers.
The study found a 24 percent overall decline in first-time strokes in each of the last two decades and a 20 percent overall drop per decade in deaths after stroke. However, the decline in stroke risk was concentrated mainly in the over-65 set, with little progress in reducing the risk of strokes among young people. In contrast, the drop in stroke-related deaths each decade was primarily found among ...
Physicians struggle to clinically diagnose early HIV infection
2014-07-15
Despite the belief that early HIV infection presents with a well recognized flu-like syndrome, most physicians are unable to use clinical skills to differentiate those who should and should not be tested for HIV infection, according to a study published July 15 in Journal of the American Medical Association (JAMA).
Researchers at the BC Centre for Excellence in HIV/AIDS and University of British Columbia, Oregon Health and Science University, and Duke University Medical Centre analyzed data from over 24,000 patients, and discovered physicians have great difficulty recognizing ...
Study finds decrease in incidence of stroke, subsequent death
2014-07-15
In a study that included a large sample of black and white U.S. adults from several communities, rates of stroke incidence and subsequent death decreased from 1987 to 2011, with decreases varying across age-groups, according to a study in the July 16 issue of JAMA.
Stroke ranks fourth among all causes of death in the U.S. and is recognized as a leading cause of serious physical and cognitive long-term disability in adults. Almost 800,000 Americans suffer a stroke each year, and over 600,000 of them are first-ever events. Stroke incidence varies by gender and ethnic group, ...
Telecare intervention improves chronic pain
2014-07-15
A telephone-delivered intervention, which included automated symptom monitoring, produced clinically meaningful improvements in chronic musculoskeletal pain compared to usual care, according to a study in the July 16 issue of JAMA.
Pain is the most common symptom reported both in the general population and patients seen in primary care, the leading cause of work disability, and a condition that costs the United States more than $600 billion each year in health care and lost productivity. Musculoskeletal pain accounts for nearly 70 million outpatient visits annually in ...
History of stroke linked with increased risk of adverse outcomes after non-cardiac surgery
2014-07-15
In an analysis that included more than 480,000 patients who underwent elective noncardiac surgery, a history of stroke was associated with an increased risk of major adverse cardiovascular events and death, particularly if time elapsed between stroke and surgery was less than 9 months, according to a study in the July 16 issue of JAMA.
Noncardiac surgeries performed in patients with a recent heart attack or stent implantation have been associated with increased risk of perioperative cardiac events, as well as stent thrombosis (blood clot), and bleeding compared with ...
Physicians have higher rate of organ donation registration than general public
2014-07-15
A study that included about 15,000 physicians found that they were more likely to be registered as an organ donor compared to the general public, according to a study in the July 16 issue of JAMA.
A shortage of organs for transplant has prompted many countries to encourage citizens to register ("opt in") to donate their organs and tissues when they die. However, less than 40 percent of the public is registered for organ donation in most countries with a registry. "One common fear is that physicians will not take all measures to save the life of a registered citizen at ...
Common treatment of certain autoimmune disease does not appear effective
2014-07-15
Among patients with the systemic autoimmune disease primary Sjögren syndrome, use of hydroxychloroquine, the most frequently prescribed treatment for the disorder, did not improve symptoms during 24 weeks of treatment compared with placebo, according to a study in the July 16 issue of JAMA.
Primary Sjögren syndrome is characterized by mouth and eye dryness, pain, and fatigue, with systemic manifestations occurring in approximately one-third of patients. Despite the wide use of hydroxychloroquine in clinical practice, evidence regarding its efficacy is limited, according ...
JAMA study: Telecare program optimizing non-opioid chronic pain medication very effective
2014-07-15
INDIANAPOLIS -- Chronic pain in the back, neck and other joints due to arthritis or other musculoskeletal disorders is extremely common but difficult to treat. In a new study published in the July 16 issue of Journal of the American Medical Association, primary-care patients enrolled in a 12-month telecare program optimizing non-opioid medications for chronic pain were twice as likely to see improvement as patients who received usual care for chronic pain.
In addition to experiencing pain improvement, patients in the telecare arm of the pain management study reported ...
Do daughters really cause divorce? Maybe not
2014-07-15
DURHAM, N.C. -- In the U.S., couples with daughters are somewhat more likely to divorce than couples with sons. Many scholars have read those numbers as evidence that daughters cause divorce.
But new research from Duke University suggests something quite different may be at play: Girls may be hardier than boys, even in the womb, and may be better able to survive pregnancies stressed by a troubled marriage.
Previous studies have argued that fathers prefer boys and are more likely to stay in marriages that produce sons. Conversely, the argument runs, men are more likely ...
Gene discovery could lead to better soybean varieties for Northern United States
2014-07-15
WEST LAFAYETTE, Ind. – Researchers from Purdue University and the University of Nebraska-Lincoln have discovered a soybean gene whose mutation affects plant stem growth, a finding that could lead to the development of improved soybean cultivars for the northern United States.
Purdue agronomy professor Jianxin Ma (pronounced Jen-SHIN' Ma) and collaborators identified a gene known as Dt2, which causes semideterminacy in soybean plants. Semideterminate soybean plants - mid-size plants that continue vegetative growth even after flowering - can produce as many or more pods ...