Posts tagged alzheimer

Scientists at Washington University School of Medicine in St. Louis have taken one of the first detailed looks into how Alzheimer’s disease disrupts coordination among several of the brain’s networks. The results, reported in The Journal of Neuroscience, include some of the earliest assessments of Alzheimer’s effects on networks that are active when the brain is at rest.

“Until now, most research into Alzheimer’s effects on brain networks has either focused on the networks that become active during a mental task, or the default mode network, the primary network that activates when a person is daydreaming or letting the mind wander,” says senior author Beau Ances, MD, assistant professor of neurology. “There are, however, a number of additional networks besides the default mode network that become active when the brain is idling and could tell us important things about Alzheimer’s effects.”

Ances and his colleagues analyzed brain scans of 559 subjects. Some of these subjects were cognitively normal, while others were in the early stages of very mild to mild Alzheimer’s disease. Scientists found that all of the networks they studied eventually became impaired during the initial stages of Alzheimer’s.

“Communications within and between networks are disrupted, but it doesn’t happen all at once,” Ances says. “There’s even one network that has a momentary surge of improved connections before it starts dropping again. That’s the salience network, which helps you determine what in your environment you need to pay attention to.”

Other networks studied by the researchers included:

• the dorsal attention network, which directs attention toward things in the environment that are salient;

• the control network, believed to be active in consciousness and decision-making; and

• the sensory-motor network, which integrates the brain’s control of body movements with sensory feedback (e.g., did the finger that just moved strike the right piano key?).

Scientists also examined Alzheimer’s effects on a brain networking property known as anti-correlations. Researchers identify networks by determining which brain areas frequently become active at the same time, but anti-correlated networks are noteworthy for the way their activities fluctuate: when one network is active, the other network is quiet. This ability to switch back-and-forth between networks is significantly diminished in participants with mild to moderate Alzheimer’s disease.

The default mode network, previously identified as one of the first networks to be impaired by Alzheimer’s, is a partner in two of the three pairs of anti-correlated networks scientist studied.

“While we can’t prove this yet, one hypothesis is that as things go wrong in the processing of information in the default mode network, that mishandled data is passed on to other networks, where it creates additional problems,” Ances says.

It’s not practical to use these network breakdowns to clinically diagnose Alzheimer’s disease, Ances notes, but they may help track the development of the disease and aid efforts to better understand its spread through the brain.

Ances plans to look at other markers for Alzheimer’s disease in the same subjects, such as levels in the cerebrospinal fluid of amyloid beta, a major component of Alzheimer’s plaques.

(Source: news.wustl.edu)

An enzyme that could represent a powerful new tool for combating Alzheimer’s disease has been discovered by researchers at Mayo Clinic in Florida. The enzyme — known as BACE2 — destroys beta-amyloid, a toxic protein fragment that litters the brains of patients who have the disease. The findings were published online Sept. 17 in the science journal Molecular Neurodegeneration.

Alzheimer’s disease is the most common memory disorder. It affects more that 5.5 million people in the United States. Despite the disorder’s enormous financial and personal toll, effective treatments have not yet been found.

The Mayo research team, led by Malcolm A. Leissring, Ph.D., a neuroscientist at Mayo Clinic in Florida, made the discovery by testing hundreds of enzymes for the ability to lower beta-amyloid levels. BACE2 was found to lower beta-amyloid more effectively than all other enzymes tested. The discovery is interesting because BACE2 is closely related to another enzyme, known as BACE1, involved in producing beta-amyloid.

“Despite their close similarity, the two enzymes have completely opposite effects on beta-amyloid — BACE1 giveth, while BACE2 taketh away,” Dr. Leissring says.

Beta-amyloid is a fragment of a larger protein, known as APP, and is produced by enzymes that cut APP at two places. BACE1 is the enzyme responsible for making the first cut that generates beta-amyloid. The research showed that BACE2 cuts beta-amyloid into smaller pieces, thereby destroying it, instead. Although other enzymes are known to break down beta-amyloid, BACE2 is particularly efficient at this function, the study found.

Previous work had shown that BACE2 can also lower beta-amyloid levels by a second mechanism: by cutting APP at a different spot from BACE1. BACE2 cuts in the middle of the beta-amyloid portion, which prevents beta-amyloid production.

“The fact that BACE2 can lower beta-amyloid by two distinct mechanisms makes this enzyme an especially attractive candidate for gene therapy to treat Alzheimer’s disease,” says first author Samer Abdul-Hay, Ph.D., a neuroscientist at Mayo Clinic in Florida.

The discovery suggests that impairments in BACE2 might increase the risk of Alzheimer’s disease. This is important because certain drugs in clinical use — for example, antiviral drugs used to treat human immunodeficiency virus (HIV) — work by inhibiting enzymes similar to BACE2.

Although BACE2 can lower beta-amyloid by two distinct mechanisms, only the newly discovered mechanism — beta-amyloid destruction — is likely relevant to the disease, the researchers note. This is because the second mechanism, which involves BACE2 cutting APP, does not occur in the brain. The researchers have obtained a grant from the National Institutes of Health to study whether blocking beta-amyloid destruction by BACE2 can increase the risk for Alzheimer’s disease in a mouse model of the disease.

(Source: newswise.com)

A drug designed for diabetes sufferers could have the potential to treat neurodegenerative diseases like Alzheimer’s, a study by scientists at the University of Ulster has revealed.

Type II diabetes is a known risk factor for Alzheimer’s and it is thought that impaired insulin signalling in the brain could damage nerve cells and contribute to the disease.

Scientists believe that drugs designed to tackle Type II diabetes could also have benefits for keeping our brain cells healthy.

To investigate this, Prof Christian Hölscher and his team at the Biomedical Sciences Research Institute on the Coleraine campus used an experimental drug called (Val8)GLP-1.

This drug simulates the activity of a protein called GLP-1, which can help the body control its response to blood sugar. The scientists treated healthy mice with the drug and studied its effects in the brain.

Although it is often difficult for drugs to cross from the blood into the brain, the team found that (Val8)GLP-1 entered the brain and appeared to have no side-effects at the doses tested.

The drug promoted new brain cells to grow in the hippocampus, an area of the brain known to be involved in memory. This finding suggests that as well as its role in insulin signalling, GLP-1 may also be important for the production of new nerve cells in the mouse brain.

The team found that blocking the effect of GLP-1 in the brain made mice perform more poorly on learning and memory task, while boosting it with the drug seemed to have no effect on behaviour.

The new findings, published this week in the journal Brain Research, are part of ongoing research funded by Alzheimer’s Research UK, the leading dementia research charity.

Prof Hölscher, said: “Here at the Biomedical Sciences Research Institute, we are really interested in the potential of diabetes drugs for protecting brain cells from damage and even promoting new brain cells to grow. This could have huge implications for diseases like Alzheimer’s or Parkinson’s, where brain cells are lost.

“It is very encouraging that the experimental drug we tested, (Val8)GLP-1, entered the brain and our work suggests that GLP-1 could be a really important target for boosting memory. While we didn’t see benefits on learning and memory in these healthy mice, we are keen to test the drugs in mice with signs of Alzheimer’s disease, where we could see real improvements.”

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said: “We are pleased to have supported this early stage research, suggesting that this experimental diabetes drug could also promote the growth of new brain cells. While we know losing brain cells is a key feature of Alzheimer’s, there is a long way to go before we would know whether this drug could benefit people with the disease.

"This research will help us understand the factors that keep nerve cells healthy, knowledge that could hold vital clues to tackling Alzheimer’s. With over half a million people in the UK living with the disease, learning more about how to keep our brain cells healthy is of vital importance. Funding for dementia research lags far behind that of other common diseases, but is essential if we are to realise the true potential of research like this.”

(Source: alphagalileo.org)

Executive function tests key to early detection of Alzheimer’s, Concordia study shows

By the time older adults are diagnosed with Alzheimer’s disease, the brain damage is irreparable. For now, modern medicine is able to slow the progression of the disease but is incapable of reversing it. What if there was a way to detect if someone is on the path to Alzheimer’s before substantial and non-reversible brain damage sets in?

This was the question Erin K. Johns, a doctoral student in Concordia University’s Department of Psychology and member of the Center for Research in Human Development (CRDH), asked when she started her research on older adults with mild cognitive impairment (MCI). These adults show slight impairments in memory, as well as in “executive functions” like attention, planning, and problem solving. While the impairments are mild, adults with MCI have a high risk of developing Alzheimer’s disease.

“We wanted to help provide more reliable tools to identify people who are at increased risk for developing Alzheimer’s so that they can be targeted for preventive strategies that would stop brain damage from progressing,” says Johns.

The new study was published in the Journal of the International Neuropsychological Society and was funded by the Quebec Network for Research on Aging and the Canadian Institutes of Health Research. In it, Johns and her colleagues found that people with MCI are impaired in several aspects of executive functioning, the biggest being inhibitory control. 

This ability is crucial for self-control: everything from resisting buying a candy bar at the checkout aisle to resisting the urge to mention the obvious weight gain in a relative you haven’t seen in a while. Adults with MCI also had trouble with tests that measure the ability to plan and organize.

Johns and her colleagues found that all the adults with MCI they tested were impaired in at least one executive function and almost half performed poorly in all the executive function tests. This is in sharp contrast with standard screening tests and clinical interviews, which detected impairments in only 15 percent of those with MCI.

“The problem is that patients and their families have difficulty reporting executive functioning problems to their physician, because they may not have a good understanding of what these problems look like in their everyday life.” says Johns. “That’s why neuropsychological testing is important.”

Executive function deficits affect a person’s everyday life and their ability to plan and organize their activities. Even something as easy as running errands and figuring out whether to go to the drycleaners or to the supermarket can be difficult for adults with MCI. Detecting these problems early could improve patient care and treatment planning.

“If we miss the deficits, we miss out on an opportunity to intervene with the patient and the family to help them know what to expect and how to cope,” says Johns. She is now conducting a follow-up study funded by the Alzheimer Society of Canada and Canadian Institutes of Health Research, along with her supervisor, Natalie Phillips, associate professor in the Department of Psychology and member of CRDH.

Johns hopes her continued research will lead to a better understanding of why these deficits start at such an early stage of Alzheimer’s and what other tools could be used for earlier detection of the disease.

(Source: concordia.ca)

This week, a strategic roadmap to help to the nation’s health care system cope with the impending public health crisis caused Alzheimer’s disease and related dementia will be published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The plan aims to link the latest scientific findings with clinical care and bring together patients, families, scientists, pharmaceutical companies, regulatory agencies, and advocacy organizations behind a common set of prioritized goals. The consensus document is the outcome of a June meeting of leading Alzheimer’s researchers, advocates and clinicians, who gathered as part of the Marian S. Ware Alzheimer Program at the University of Pennsylvania.

Today, 5.4 million people are living with the disease, and more than 15 million Americans are caring for persons with Alzheimer’s and other dementias, according to the Alzheimer’s Association. Alzheimer’s disease is the sixth-leading cause of death in the United States and the only cause of death among the top 10 in the United States that cannot be prevented, cured, or even slowed.

"Our plan aims to provide good quality care for affected patients and families, advance our understanding of the pathophysiology and natural history of AD and other dementias, develop effective treatments to slow or prevent these diseases, and translate scientific advances successfully into policy and practice," the authors wrote.

(Source: nursing.upenn.edu)

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September 5, 2012 by Michael C. Purdy

Sleep disruptions may be among the earliest indicators of Alzheimer’s disease, scientists at Washington University School of Medicine in St. Louis report Sept. 5 in Science Translational Medicine.

Working in a mouse model, the researchers found that when the first signs of Alzheimer’s plaques appear in the brain, the normal sleep-wake cycle is significantly disrupted.

“If sleep abnormalities begin this early in the course of human Alzheimer’s disease, those changes could provide us with an easily detectable sign of pathology,” says senior author David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of Washington University’s Department of Neurology. “As we start to treat Alzheimer’s patients before the onset of dementia, the presence or absence of sleep problems may be a rapid indicator of whether the new treatments are succeeding.”

Holtzman’s laboratory was among the first to link sleep problems and Alzheimer’s through studies of sleep in mice genetically altered to develop Alzheimer’s plaques as they age. In a study published in 2009, he showed that brain levels of a primary ingredient of the plaques naturally rise when healthy young mice are awake and drop after they go to sleep. Depriving the mice of sleep disrupted this cycle and accelerated the development of brain plaques.

A similar rising and falling of the plaque component, a protein called amyloid beta, was later detected in the cerebrospinal fluid of healthy humans studied by co-author Randall Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University.

The new research, led by Jee Hoon Roh, MD, PhD, a neurologist and postdoctoral fellow in Holtzman’s laboratory, shows that when the first indicators of brain plaques appear, the natural fluctuations in amyloid beta levels stop in both mice and humans.

“We suspect that the plaques are pulling in amyloid beta, removing it from the processes that would normally clear it from the brain,” Holtzman says.

Mice are nocturnal animals and normally sleep for 40 minutes during every hour of daylight, but when Alzheimer’s plaques began forming in their brains, their average sleep times dropped to 30 minutes per hour.

To confirm that amyloid beta was directly linked to the changes in sleep, researchers gave a vaccine against amyloid beta to a new group of mice with the same genetic modifications. As these mice grew older, they did not develop brain plaques. Their sleeping patterns remained normal and amyloid beta levels in the brain continued to rise and fall regularly.

Scientists now are evaluating whether sleep problems occur in patients who have markers of Alzheimer’s disease, such as plaques in the brain, but have not yet developed memory or other cognitive problems.

“If these sleep problems exist, we don’t yet know exactly what form they take—reduced sleep overall or trouble staying asleep or something else entirely,” Holtzman says. “But we’re working to find out.”

(Source: news.wustl.edu)