New study shows how patterns in brain activity can be an early predictor of Alzheimer’s symptoms
SAN FRANCISCO, November 19, 2019 (Newswire.com) – For a person with Alzheimer’s disease, there’s no turning back the clock. By the time she begins to experience memory loss and other worrisome signs, cognitive decline has already set in. And decades of clinical trials have failed to produce treatments that could help her regain her memory. Today, researchers at Gladstone Institutes are approaching this devastating disease from a different angle.
In a new study published in Cell Reports, they demonstrate that particular patterns of brain activity can predict far in advance whether a young mouse will develop Alzheimer’s-like memory deficits in old age.
“Being able to predict deficits long before they appear could open up new opportunities to design and test interventions that prevent Alzheimer’s in people,” said Gladstone Senior Investigator Yadong Huang, senior author of the study.
The new work builds on a 2016 study of mice engineered to carry the gene for apolipoprotein E4 (ApoE4). Carrying the ApoE4 gene is associated with an increased risk — but not a guarantee — of Alzheimer’s disease in humans. As they age, ApoE4 mice often, but not always, develop signs of memory loss similar to those seen in people with Alzheimer’s.
In the previous study, Huang and his team investigated a type of brain activity called sharp-wave ripples (SWRs), which play a direct role in spatial learning and memory formation in mammals. SWRs occur when the brain of a resting mouse or human rapidly and repeatedly replays a recent memory of moving through a space, such as a maze or a house.
“SWRs have two important measurable components: abundance and short gamma (SG) power,” said Emily Jones, Ph.D., lead author of the new study and recent graduate of UC San Francisco’s (UCSF) Biomedical Sciences Graduate Program. “Broadly, SWR abundance predicts how quickly an ApoE4 mouse can learn and memorize how to get through a maze, and SG power predicts how accurate that memory will be.”
The earlier study revealed that aging ApoE4 mice have lower SWR abundance and weaker SG power than seen in healthy aging mice. Based on those results, Jones and her colleagues hypothesized that measuring SWR activity could predict the severity of demonstrable memory problems in ApoE4 mice during aging.
To test this idea, the researchers first recorded SWR activity in aging ApoE4 mice at rest. One month later, they had the mice perform spatial tasks to test their memory. They found that mice with fewer SWRs and lower SG power were indeed more likely to have worse spatial memory deficits.
“We actually successfully replicated this experiment two years later with different mice,” said Huang, who is also a professor of neurology and pathology at UCSF. “What was striking is that we were able to use the results from the first cohort to predict with high accuracy the extent of learning and memory deficits in the second cohort, based on their SWR activity.”
Even more striking were the unexpected results of the team’s next experiment.
The researchers were curious how SWR activity evolves over a mouse’s lifetime, which no one had previously investigated. So, they periodically measured SWRs in ApoE4 mice from an early age — long before memory deficits appeared — through middle age and into old age.
“We thought that, if we got lucky, the SWR measurements we took when the mice were middle-aged might have some predictive relationship to later memory problems,” Jones said.
Surprisingly, the analysis revealed that deficits in SWR abundance and SG power at an early age predicted which mice performed worse on memory tasks 10 months later — the equivalent of 30 years for a human.
“We were not betting on these results, the idea that young mice with no memory problems already have the seed of what’s going to lead to deficits in old age,” Jones said. “Although we would love to, but we thought it would be ridiculous to be able to predict so far in advance.”
Since SWRs are also found in humans, these findings suggest that SWR abundance and SG power could potentially serve as early predictors of Alzheimer’s disease, long before memory problems arise.
As a next step toward evaluating that possibility, Huang will work with colleagues at the UCSF Memory and Aging Center to determine whether SWRs in Alzheimer’s patients show deficits in abundance and SG power similar to those seen in mouse models of the disease.
“A major advantage of this approach is that researchers have recently developed a noninvasive technique for measuring SWRs in people, without implanting electrodes in the brain,” Huang said.
If SWRs are indeed predictive of Alzheimer’s in humans, measuring them could boost research and drug development efforts in two important ways. First, they could be used to select participants for clinical trials, testing new drugs to stave off Alzheimer’s. Enrolling patients who already show SWR deficits would enhance the trials’ statistical power. Second, SWR measurements could be taken repeatedly and noninvasively, enabling researchers to test drug effects over time, even before memory deficits appear.
Huang emphasizes the value of SWRs as a functional predictor, one that directly measures the decline in brain function seen in Alzheimer’s, as opposed to a pathological change that only appears as a result of the underlying disease.
“I feel strongly that Alzheimer’s research should not just focus on pathology but use functional alterations like SWR deficits to guide research and drug development,” he said. “Our new findings support this kind of approach.”
The new study is just one facet of Gladstone’s extensive Alzheimer’s research program. “Gladstone provides a unique setting that makes it possible to do the kind of translational research necessary to improve understanding and treatment of this disease,” Huang said.
About the Research Project
Other authors include Anna Gillespie, Ph.D., from UCSF; Seo Yeon Yoon from Gladstone; and Loren Frank, Ph.D., from UC San Francisco and the Howard Hughes Medical Institutes.
The work was supported by a National Science Foundation Graduate Research Fellowship (grant 1144247), a National Institute on Aging Predoctoral Fellowship (grant F31AG057150), a Genentech Foundation Fellowship, a Simons Collaboration for the Global Brain Fellowship, the Howard Hughes Medical Institute, and the National Institute on Aging (grants RF1AG047655, RF1AG055421, and R01AG055682).
About the Gladstone Institutes
To ensure our work does the greatest good, the Gladstone Institutes focuses on conditions with profound medical, economic, and social impact — unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.
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Source: Gladstone Institutes
New study shows how patterns in brain activity can be an early predictor of Alzheimer’s symptoms
…medical researchers worldwide are collaborating in hope of discovering a greater understanding of Alzheimer’s in order to ultimately find a remedy or preventive measure for the illness conduct an extensive level of scientific inquiry.
MIAMI (PRWEB) November 08, 2019
“The Matrix”, “Deep Cover”, and “John Wick” series star Laurence Fishburne is the host of the educational television program “Behind The Scenes”. This informational program seeks to inform its public audience about a myriad of topics affecting people all over the world today. In an impending episode of “Behind The Scenes,” the show will explore a topic within the world of medical research. The episode will highlight medical professionals as they delve into the effects of Alzheimer’s disease.
This specific episode will explore the medical developments in the field of Alzheimer’s disease research and will discuss the impact of the ailment on those suffering with it. Alzheimer’s disease is a debilitating form of dementia affecting thousands of Americans every day. On average, an individual diagnosed with the affliction has a life span of four to eight years after they are given their prognosis. Affecting memory loss and multiple cognitive abilities, the disease takes a heavy toll on performing daily tasks and quality of life.
Alzheimer’s disease is one of the top contributors of death in the United States today. Currently the condition has no cure. However, medical researchers worldwide are collaborating in hope of discovering a greater understanding of Alzheimer’s in order to ultimately find a remedy or preventive measure for the illness conduct an extensive level of scientific inquiry. The segment will feature leaders in the field to discuss these developments.
“Behind The Scenes” with Laurence Fishburne is a carefully reviewed television program prior to being broadcast to a larger viewing audience. The show has received a multitude of awards in recognition of its work.
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$4.5 Million to Study How Neurovascular Dysfunction Contributes to Neurodegeneration in Alzheimer's Disease
NIH award supports collaborative work to discover the connection between neurovascular dysfunction and cognitive decline in Alzheimer’s disease.
Press Release – updated: Oct 31, 2019 13:59 PDT
SAN FRANCISCO, October 31, 2019 (Newswire.com) – Alzheimer’s disease is a progressive neurodegenerative disease that causes loss of memory. Despite decades of research into how the disease causes brain cells to die, there is no cure.
In the last several years, a string of clinical trials for Alzheimer’s disease therapies have failed. These failures suggest that scientists need to take a fresh look at what drives Alzheimer’s disease to design new approaches.
Researchers at Gladstone Institutes are doing just that. A team led by Senior Investigator Katerina Akassoglou was recently awarded over $4.5 million from the National Institutes of Health (NIH) to study how dysfunction of blood vessels in the brain (the neurovascular system) can lead to neurodegeneration.
“There is an emerging interest in the contribution of vascular dysfunction to Alzheimer’s disease. We know that in Alzheimer’s disease, changes to blood vessels in the brain occur really early, and they correlate and often precede dementia,” explained Akassoglou, who is also a professor of neurology at UC San Francisco.
However, whether and how this vascular dysfunction causes cognitive decline remains a mystery.
Akassoglou and her team previously showed that one consequence of vascular dysfunction is that proteins normally found in the blood can leak into the brain due to a compromised blood-brain barrier. Specifically, their research pinpointed a damaging effect of fibrinogen, a blood protein important for clotting, that is deposited in the brains of Alzheimer’s disease patients. When fibrinogen escapes the blood vessels and enters the brain, it can activate the brain’s immune cells and trigger them to destroy important connections between neurons, hastening the loss of synapses and entire nerve cells.
Another finding that has emerged from recent research is that the activity of neurons—the rate and rhythm with which they fire—is altered in the brains of Alzheimer’s disease patients. Research from Gladstone investigators Jorge Palop and Lennart Mucke has shown that these changes to neuronal activity can occur decades before the onset of Alzheimer’s symptoms. Alzheimer’s-associated changes in neuronal activity also include seizures.
This new NIH grant will support Akassoglou, Palop, and a third collaborator, Mark Ellisman, at UC San Diego, as they join forces to investigate whether these two aspects of Alzheimer’s disease—vascular dysfunction and excessive neuronal activity—are related, and whether blocking one can prevent the other.
“How dysfunction of the vascular and immune systems alters ongoing neuronal activity is a critical question in the study of Alzheimer’s disease,” said Palop. “We can record brain electrical activity in a mouse for weeks at a time and observe how vascular damage affects neuronal function.”
“We know that the vascular alterations and blood leaks are present in Alzheimer’s disease, but we do not know how they affect neuronal activity,” said Akassoglou. “Connecting the dots between blood leaks, the brain’s immune cells, and neuronal activity could change the way we think how cognitive decline develops and be the cornerstone for developing new treatments.”
The project builds on a long-running collaboration between Akassoglou and Ellisman, a distinguished professor at UC San Diego School of Medicine and an expert in multiscale microscopy. Ellisman is the director of the National Center for Microscopy and Imaging Research, and is a pioneer in the development of 3-dimensional light and electron microscopy applied to the study of the structure and function of normal and abnormal nervous systems.
By combining state-of-the-art imaging techniques with recordings of neuronal activity, the researchers hope to discover the series of events that lead to cognitive decline in Alzheimer’s disease. They also hope to identify new therapeutic targets that might prevent this process.
“It’s critical to understand the relationships between vascular, neuronal, and immune dysfunctions,” said Lennart Mucke, director of the Gladstone Institute of Neurological Disease. “This work and related studies by other groups in our institute will be invaluable in the design of novel therapies for Alzheimer’s disease and a range of other impactful brain disorders.”
About Gladstone InstitutesTo ensure our work does the greatest good, the Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.
Source: Gladstone Institutes
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