New Mechanism Behind Alzheimer’s Onset Identified

(Medical News Today) A new study published in the journal Brain overturns thinking on the role of toxic peptides in the development of Alzheimer’s disease.

Sporadic Alzheimer’s disease accounts for 99% of all Alzheimer’s cases, and involves the development of toxic peptide deposits in the brain. These peptide deposits cause the neuronal networks to be destroyed, leading to disorientation, memory loss, changes in behavior and death.

Although studies of Alzheimer’s in animal models typically use mice with mutated human genes, the new study – conducted by researchers at the University of Oslo in Norway – used a new mouse model for the more common sporadic form of Alzheimer’s.

To create this new mouse model, the function was removed from two genes in the brain that are used to excrete and digest toxic Alzheimer’s peptide beta-amyloid. The researchers say this new “transgene-free” mouse model allows studies to be conducted without “artificial overexpression” of inherited Alzheimer’s disease genes.

Although it has previously been assumed that overproduction of toxic peptides causes the onset and first clinical signs of Alzheimer’s, the new study finds that the responsible mechanism is decreased removal of toxic peptides, rather than overproduction.

The team observed that insufficient removal of toxic metabolites in the mouse model was associated with early signs of Alzheimer’s in the precise brain locations where these changes appear in humans with the disease.
Memory loss ‘not always first sign of Alzheimer’s’

In other Alzheimer’s news, a study published in the journal Alzheimer’s & Dementia and conducted by researchers at the National Hospital for Neurology and Neurosurgery in London, UK, suggests that memory loss may not always be the first sign of Alzheimer’s, as is commonly believed.

Reviewing neurology test results from a large US sample of Alzheimer’s patients, the UK team found that 1 in 5 patients in their 60s cited early symptoms unrelated to memory, although only 1 in 10 patients in their 70s had early difficulties other than memory problems.

In other words, the proportion of patients who cited early problems that were not memory related shrank with age.

Lead study author Josephine Barnes told Reuters:

“Non-memory first cognitive symptoms were more common in younger Alzheimer’s disease patients. Tests which explore and investigate these non-memory cognitive problems should be used so that non-memory deficits are not overlooked.”

Another recent Alzheimer’s study using a mouse model, which Medical News Today looked at last month, reported some success in blocking the production of beta-amyloid, which could potentially stop the disease in its tracks with minimal side effects. Mice who received the new treatment exhibited a 50% or more reduction in amyloid plaque accumulation.


Written by David McNamee

MediLexicon International Ltd, Bexhill-on-Sea, UK

© 2004-2015 All rights reserved.


Green Tea Extract and Exercise Hinder Progress of Alzheimer’s Disease in Mice

(Journal of Alzheimer’s Disease) Comprehensive study of EGCG, a compound found in green tea, could lead to treatments of Alzheimer’s in humans.

According to the National Institutes of Health (NIH), Alzheimer’s disease (AD) may affect as many as 5.5 million Americans. Scientists currently are seeking treatments and therapies found in common foods that will help stave off the disease or prevent it completely.

Now, University of Missouri researchers have determined that a compound found in green tea, and voluntary exercise, slows the progression of the disease in mice and may reverse its effects. Further study of the commonly found extract could lead to advancements in the treatment and prevention of Alzheimer’s disease in humans.

“In Alzheimer’s patients, amyloid-beta peptide (A-beta) can accumulate and clump together causing amyloid plaques in the brain,” said Todd Schachtman, professor of psychological sciences in the College of Arts and Science at MU.

“Symptoms can include increased memory loss and confusion, agitation and a lack of concern for your environment and surroundings. We looked at ways of preventing or postponing the onset of the disease which we hope can eventually lead to an improvement of health status and quality of life for the elderly.”

Increases in inflammation have been linked to Alzheimer’s disease patients and recent studies have suggested the benefits of dietary antioxidants in reducing the risk of AD. Based on previous research conducted at Mizzou, researchers decided to investigate the effects of voluntary exercise and epigallocatechin-3-gallate (EGCG), a green tea extract, on memory function and A-beta levels in mice known to show plaque deposits and behavior deficits.

First, mice were placed in the center of a specialized maze and allowed to move around with the aim of finding the right hole, or “goal box.” Schachtman and his research team, including Jennifer Walker, a graduate student in psychology, and Agnes Simonyi, research associate professor in biochemistry, watched the mice to determine whether or not they could find the goal box, demonstrating memory and cognition.

In the second test, small “nestlets,” or squares containing materials to create nests, were placed in the habitats for different groups of mice. A day later, nests were scored based on shape and the amount of material used.

“Mice exhibiting symptoms of the disease had nests that were poorly formed or erratic,” said Schachtman.

“Further, we found that mice with Alzheimer’s symptoms, much like people, can be apathetic about their habitat, or have forgotten how to ‘nest’ appropriately.”

Researchers then administered EGCG in the drinking water of the mice and gave them access to running or exercise wheels. After re-administering the maze and nesting tests, they found remarkable improvements in the cognitive function and retention in the Alzheimer’s affected mice that were given EGCG and were allowed to exercise.

Finally, a team of biochemists led by Grace Sun, professor emerita of biochemistry in the School of Medicine and the College of Agriculture, Food and Natural Resources at MU, and including Walker and Deepa Ajit, a postdoctoral fellow, analyzed mouse brain tissues to determine the effects of EGCG and exercise on A-beta levels in affected regions of the brain.

“Oral administration of the extract, as well as voluntary exercise, improved some of the behavioral manifestations and cognitive impairments of Alzheimer’s,” said Sun, who also serves as the director of the Alzheimer’s Disease Program at MU funded by the National Institutes of Health.

“We also are excited to see a decrease in A-beta levels in the brains of the affected mice as well as improvements in behavior deficits in mice with AD.”

Consumption of natural products as potential remedies to prevent and treat diseases and to maintain human health is an ancient one, said Sun. Future studies of green tea extracts and other botanicals, also known as nutraceuticals, are being explored at MU and through collaborations with other international institutions.

The study, “Beneficial Effects of Dietary EGCG and Voluntary Exercise on Behavior in an Alzheimer’s Disease Mouse Model,” was published in the Journal of Alzheimer’s Disease with grant funding from the National Institute of Aging (AG018357) and NCCAM/ODS/NCI (AT006273). The content is solely the responsibility of the authors and does not necessarily represent the official views of either funding agency.


Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2015


Poor Sleep Linked to Toxic Buildup of Alzheimer’s Protein, Memory Loss

(University of Berkeley) Sleep may be a missing piece in the Alzheimer’s disease puzzle.

Scientists at the University of California, Berkeley, have found compelling evidence that poor sleep — particularly a deficit of the deep, restorative slumber needed to hit the save button on memories — is a channel through which the beta-amyloid protein believed to trigger Alzheimer’s disease attacks the brain’s long-term memory.

“Our findings reveal a new pathway through which Alzheimer’s disease may cause memory decline later in life,” said UC Berkeley neuroscience professor Matthew Walker, senior author of the study to be published in the journal Nature Neuroscience.

Excessive deposits of beta-amyloid are key suspects in the pathology of Alzheimer’s disease, a virulent form of dementia caused by the gradual death of brain cells. An unprecedented wave of aging baby boomers is expected to make Alzheimer’s disease, which has been diagnosed in more than 40 million people, one of the world’s fastest-growing and most debilitating public health concerns.

AmyloidBurden400Heavy deposits of the toxic protein, beta-amyloid, shown in red in the brain on the right, are linked to poor sleep and may be paving the way for Alzheimer’s disease. A brain benefiting from deep sleep brain waves and an absence of beta-amyloid is shown on the left. (Photo courtesy of Bryce Mander and Matthew Walker)

The good news about the findings, Walker said, is that poor sleep is potentially treatable and can be enhanced through exercise, behavioral therapy and even electrical stimulation that amplifies brain waves during sleep, a technology that has been used successfully in young adults to increase their overnight memory.

“This discovery offers hope,” he said. “Sleep could be a novel therapeutic target for fighting back against memory impairment in older adults and even those with dementia.”

The study was co-led by UC Berkeley neuroscientists Bryce Mander and William Jagust, a leading expert on Alzheimer’s disease. The team has received a major National Institutes of Health grant to conduct a longitudinal study to test their hypothesis that sleep is an early warning sign or biomarker of Alzheimer’s disease.

Bryce Mander demonstrates how a 2013 study linking poor sleep to memory loss was conducted. (UC Berkeley video by Roxanne Makasdjian)

While most research in this area has depended on animal subjects, this latest study has the advantage of human subjects recruited by Jagust, a professor with joint appointments at UC Berkeley’s Helen Wills Neuroscience Institute, the School of Public Health and the Lawrence Berkeley National Laboratory.

“Over the past few years, the links between sleep, beta-amyloid, memory, and Alzheimer’s disease have been growing stronger,” Jagust said. “Our study shows that this beta-amyloid deposition may lead to a vicious cycle in which sleep is further disturbed and memory impaired.”

Using a powerful combination of brain imaging and other diagnostic tools on 26 older adults who have not been diagnosed with dementia, researchers looked for the link between bad sleep, poor memory and the toxic accumulation of beta-amyloid proteins.

“The data we’ve collected are very suggestive that there’s a causal link,” said Mander, lead author of the study and a postdoctoral researcher in the Sleep and Neuroimaging Laboratory directed by Walker. “If we intervene to improve sleep, perhaps we can break that causal chain.”

A buildup of beta-amyloid has been found in Alzheimer’s patients and, independently, in people reporting sleep disorders. Moreover, a 2013 University of Rochester study found that the brain cells of mice would shrink during non-rapid-eye-movement (non-REM) sleep to make space for cerebrospinal fluids to wash out toxic metabolites such as beta-amyloid.

“Sleep is helping wash away toxic proteins at night, preventing them from building up and from potentially destroying brain cells,” Walker said. “It’s providing a power cleanse for the brain.”

Specifically, the researchers looked at how the quantity of beta-amyloid in the brain’s medial frontal lobe impairs deep non-REM sleep, which we need to retain and consolidate fact-based memories.

In a previous study, Mander, Jagust and Walker found that the powerful brain waves generated during non-REM sleep play a key role in transferring memories from the hippocampus — which supports short-term storage for information — to longer-term storage in the frontal cortex. In elderly people, deterioration of this frontal region of the brain has been linked to poor-quality sleep.

For this latest study, researchers used positron emission tomography (PET) scans to measure the accumulation of beta-amyloid in the brain; functional Magnetic Resonance Imaging (fMRI) to measure activity in the brain during memory tasks; an electroencephalographic (EEG) machine to measure brain waves during sleep; and statistical models to analyze all the data.

The research was performed on 26 older adults, between the ages of 65 and 81, who showed no existing evidence of dementia or other neurodegenerative, sleep or psychiatric disorders. First, they each received PET scans to measure levels of beta-amyloid in the brain, after which they were tasked with memorizing 120 word pairs, and then tested on how well they remembered a portion of them.

The study participants then slept for eight hours, during which EEG measured their brain waves. The following morning, their brains were scanned using fMRI as they recalled the remaining word pairs. At this point, researchers tracked activity in the hippocampus, where memories are temporarily stored before they are transferred to the prefrontal cortex.

“The more you remember following a good night of sleep, the less you depend on the hippocampus and the more you use the cortex,” Walker said. “It’s the equivalent of retrieving files from the safe storage site of your computer’s hard drive, rather than the temporary storage of a USB stick.”

Overall, the results showed that the study participants with the highest levels of beta-amyloid in the medial frontal cortex had the poorest quality of sleep and, consequently, performed worst on the memory test the following morning, with some forgetting more than half of the information they had memorized the previous day.

“The more beta-amyloid you have in certain parts of your brain, the less deep sleep you get and, consequently, the worse your memory,” Walker said. “Additionally, the less deep sleep you have, the less effective you are at clearing out this bad protein. It’s a vicious cycle.

“But we don’t yet know which of these two factors — the bad sleep or the bad protein — initially begins this cycle. Which one is the finger that flicks the first domino, triggering the cascade?” Walker added.

And that’s what the researchers will determine as they track a new set of older adults over the next five years.

“This is a new pathway linking Alzheimer’s disease to memory loss, and it’s an important one because we can do something about it,” Mander said.


Journal Reference:

Matthew P Walker et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nature Neuroscience, June 2015 DOI: 10.1038/nn.4035

Copyright © 2015 UC Regen


Amyloid Beta Causes Memory Loss Before Other Signs of Alzheimer’s Begin

(Neuroscience News) A brain protein believed to be a key component in the progress of dementia can cause memory loss in healthy brains even before physical signs of degeneration appear according to new University of Sussex research.

The study, published May 29 in the open access Nature Publishing Group journal Scientific Reports, reveals a direct link between the main culprit of Alzheimer’s disease and memory loss.

Alzheimer’s disease is characterized by the formation of amyloid plaques in the brain tissue. These amyloid plaques are made up of an insoluble protein, ‘Amyloid-beta’ (Abeta), which forms small structures called ‘oligomers’ that are important in the disease progression.

amyloid-beta-memory-loss-publicThe researchers propose that Abeta alone is enough to lead to the symptoms of memory loss that are well known in Alzheimer’s disease. The image is for illustrative purposes only. Image credit: NIA/NIH.

Although these proteins are known to be involved in Alzheimer’s, little is understood about how they lead to memory loss.

Sussex Neuroscience researchers investigated how Abeta affected healthy brains of pond snails (Lymnaea stagnalis) by observing the effect of administering the protein following a food-reward training task.

The results showed that snails treated with Abeta had significantly impaired memories 24 hours later when tested with the food task, even though their brain tissue showed no sign of damage.

Lead author on the study Lenzie Ford said this demonstrated that Abeta alone is enough to lead to the symptoms of memory loss that are well known in Alzheimer’s disease.

She said,

‘what we observed was that snail brains remained apparently healthy even after the application of the protein. There was no loss of brain tissue, no signs of cell death, no changes in the normal behaviour of the animals, and yet memory was lost.

‘This shows that Alzheimer’s amyloid proteins don’t just affect memory by killing neurons of the brain, they seem to be targeting specific molecular pathways necessary for memories to be preserved.’

Professor George Kemenes, a Sussex neuroscientist who pioneered a thorough understanding of the molecular mechanisms of learning and memory in the pond snail’s nervous system, said,

‘because we understand the memory pathways so well, the simple snail brain has provided the ideal model system to enable us to link the loss of established memory to pure Abeta’.

The work will provide a platform for a more thorough investigation of the mechanisms and effects on memory pathways that lead to this memory loss.

Professor Serpell, a senior author on the study and co-director of the University of Sussex’s Dementia Research Group, said,

‘It is absolutely essential that we understand how Alzheimer’s disease develops in order to find specific targets for therapeutics to combat this disease.’

The data used in the study, “Excess of Rare, Inherited Truncating Mutations in Autism” came from families participating in the Simons Simplex Collection and from the Simons Foundation Autism Research Initiative. The data set including millions of genetic variants, was generated in collaboration with the National Database of Autism Research , and has been made freely available to other autism researchers.

Funding: This study was funded by the Alzheimer’s Research UK, Medical Research Council, Biotechnology and Biological Sciences Research Council, Brighton and Hove City Council, and the American Friends of the University of Sussex.

Source: Jacqui Bealing – University of Sussex
Image Credit: The image is credited to NIA/NIH and is in the public domain
Original Research: Full open access research for “Effects of Aß exposure on long-term associative memory and its neuronal mechanisms in a defined neuronal network” by Lenzie Ford, Michael Crossley, Thomas Williams, Julian R. Thorpe, Louise C. Serpell and György Kemenes in Scientific Reports. Published online May 29 2015 doi:10.1038/srep10614


Effects of Aß exposure on long-term associative memory and its neuronal mechanisms in a defined neuronal network

Amyloid beta (Aβ) induced neuronal death has been linked to memory loss, perhaps the most devastating symptom of Alzheimer’s disease (AD). Although Aβ-induced impairment of synaptic or intrinsic plasticity is known to occur before any cell death, the links between these neurophysiological changes and the loss of specific types of behavioral memory are not fully understood. Here we used a behaviorally and physiologically tractable animal model to investigate Aβ-induced memory loss and electrophysiological changes in the absence of neuronal death in a defined network underlying associative memory. We found similar behavioral but different neurophysiological effects for Aβ 25-35 and Aβ 1-42 in the feeding circuitry of the snail Lymnaea stagnalis. Importantly, we also established that both the behavioral and neuronal effects were dependent upon the animals having been classically conditioned prior to treatment, since Aβ application before training caused neither memory impairment nor underlying neuronal changes over a comparable period of time following treatment.

“Effects of Aß exposure on long-term associative memory and its neuronal mechanisms in a defined neuronal network” by Lenzie Ford, Michael Crossley, Thomas Williams, Julian R. Thorpe, Louise C. Serpell and György Kemenes in Scientific Reports. Published online May 29 2015 doi:10.1038/srep10614



Memory Loss? What’s Expected and What You Can Change

(Alzheimer’s Prevention Registry)  Stay sharp! It’s the mantra of many as they age.

Collectively called cognitive abilities – clear thinking, accurate memories, sound problem-solving, and effective decision making – are the subject of a new Institute of Medicine (IOM) report. Cognitive Aging: Progress in Understanding and Opportunities for Action, aims to increase the public’s knowledge of cognitive aging as well as to clarify its misconceptions.

Cognitive aging is a lifelong process that happens to all mammals, including humans,” said Marilyn Albert, PhD, Johns Hopkins University, Professor of Neurology and Director of the Division of Cognitive Neuroscience.

Even so, cognitive aging is a source of anxiety for people as they grow older. A 2012, AARP survey revealed that staying “mentally sharp” as they age was a top concern of 87 percent of survey respondents. Much of that worry stems from fear that declines in memory or decision-making abilities may be early signs of Alzheimer’s disease.

“The IOM report makes quite a point of the fact that across a life span there can be changes in the function and capacity of the nerve cells,” said Dr. Albert, one of the experts who helped write the IOM report.

“However, cognitive aging does not lead to the death of nerve cells. With Alzheimer’s disease, one of the prominent characteristics is the death of nerve cells.”

Like all aging processes, cognitive aging varies from person to person. It’s influenced by an individual’s education level, chronic health conditions, environmental factors and early development – even in utero.

How can cognitive aging impact our lives?Day-to-day activities, such as driving, can be effected by cognitive aging. Some people have difficulty making complex financial and healthcare decisions or understanding complicated instructions given by healthcare professionals. It can become more difficult for older people to learn new things or take on highly technical or timed tasks.

Take Control of Cognitive Aging

The good news is that there are ways to address such cognitive changes. Chief among the IOM report’s recommendations is that people remain physically active. Aerobic exercise, in particular, is good for cognitive health at any age. It can even benefit people who haven’t previously been active. Aerobic exercise appears to have a direct effect on brain function but also benefits the blood vessels in the brain.

“What’s good for the heart is good for the brain,” said Dr. Albert. “I tell people if they want to maintain the brain’s vessels, they need to take care of their vascular health.”

Some of the IOM report recommendations to help minimize cognitive aging include:

  • Managing chronic health conditions (e.g., diabetes, hypertension)
  • Quitting smoking
  • Maintaining a healthy weight
  • Remaining socially engaged and involved with family and friends

“People also should be aware of the medications they’re taking and speak to their physician about whether or not their medications can affect brain function,” Dr. Albert said. “At least once a year, everyone should have a discussion about their cognitive abilities with their doctor. If there are changes that are out of the ordinary, it is important to talk to your physician about them.”

Dr. Albert emphasizes that aging also can have positive effects on cognitive abilities.

“People have more wisdom and greater ability to deal with life’s challenges,” she said.




Proteins May Slow Memory Loss in People with Alzheimer’s

(Iowa State University) Certain proteins may slow the devastating memory loss caused by Alzheimer’s disease, according to a groundbreaking Iowa State University study.

Auriel Willette, a researcher in food science and human nutrition, found evidence that an elevated presence of a protein called neuronal pentraxin-2 may slow cognitive decline and reduce brain atrophy in people with Alzheimer’s disease.

Willette will present his findings at the Psychoneuroimmunology Research Society‘s annual scientific meeting, June 3 to 6 in Seattle.

The Alzheimer’s Association predicts that by 2050, nearly 14 million Americans over 65 will have Alzheimer’s. Caring for them will cost an estimated $1 trillion every year.

“It’s just a devastating illness,” Willette said. “Unlike a lot of other neurological diseases, Alzheimer’s disease basically robs you of yourself.”

A Groundbreaking Study

Researchers have long suspected that inflammation in the brain leads to the cell death and brain atrophy found in people with Alzheimer’s disease. Yet previous studies didn’t place much emphasis on the varying roles of different immune proteins and how they might change the brain over time.

As part of his latest research, Willette analyzed data from the Alzheimer’s Disease Neuroimaging Initiative, an effort to collect and archive brain images and spinal fluid samples for researchers.

He compared brain scans, as well as fluid from the brain and spine, from three groups: people without Alzheimer’s disease, people with mild cognitive impairment or memory problems who may have Alzheimer’s disease, and people with full-blown Alzheimer’s disease.

Willette found that participants with higher levels of neuronal pentraxin-2, the protein that regulates immune function and connections between neurons, showed little or no memory loss after two years. He also found that participants with higher levels of inflammatory proteins in their cerebrospinal fluid showed modestly greater memory loss and brain atrophy over two years.

Neuronal pentraxin-2 is naturally produced in the body, primarily by neurons — nerve cells that carry electrical impulses and chemical signals. The protein seems to be involved in forming or reconfiguring connections between neurons, possibly by clearing away old debris or inefficient connections to make way for new connections.

Willette compared neuronal pentraxin-2 to a chemical bulldozer, clearing away old buildings to make way for new buildings.

“If you have high levels of this synapse-building, inflammation-regulating protein, you may not have as much, if any, change in your memory,” he said.

Reducing Risk Factors

Reducing or eliminating risk factors for brain inflammation may help prevent Alzheimer’s disease, Willette said.

People who are overweight or obese are particularly at risk of developing Alzheimer’s disease because excess body weight leads to inflammation in the brain. Exercise can help induce more activity between neurons, which could in turn boost a person’s level of neuronal pentraxin-2.

“If part of this is related to obesity, moderate exercise and reducing body weight can reduce chronic inflammation in the brain,” he said. “Exercise definitely does increase your protective factors.”

Complex jobs, hobbies, and social interactions might promote the production of protective proteins like neuronal pentraxin-2. Engaging in new or complicated cognitive tasks tends to form new or more complex connections between neurons, Willette said.

“Attaining higher levels of education, having a mentally demanding job, or regular and sustained mental effort builds something called cognitive reserve,” Willette said.

“Cognitive reserve is thought to be a protective factor against memory loss and Alzheimer’s disease. Neuronal pentraxin-2 may play a role in building cognitive reserve, helping to help create and remodel connections between neurons to handle the increased complexity thrown at the brain.”

Willette cautions against the use of nonsteroidal anti-inflammatory drugs, or pain relievers, to reduce inflammation. Researchers don’t know if these medications can help prevent the kind of inflammation associated with memory loss, and taking too many pain relievers can cause organ damage and even death.

“The literature is mixed,” he said. “Some studies find a protective effect, some do not. For people with memory loss, taking pills is also an issue. They may forget to take their pills or take too many.”

Willette hopes that future studies will look at how Alzheimer’s disease relates to body weight and epigenetics — variations in gene activity that are not caused by changes in DNA. Even if researchers are unable to find a cure for Alzheimer’s disease, slowing its symptoms could be a major help to caregivers.

“If we can slow the symptoms or halt them temporarily for even three or four years, that could have a very meaningful impact on the ability to have people live their lives as opposed to having so much of it taken up with dealing day in and day out with this disease,” Willette said.


By Meghan Brown

Copyright © 2005-2015, Iowa State University of Science and Technology. All rights reserved.


Blood Test for Alzheimer’s One Step Closer

(UNT Health Science Center) A simple blood test to detect early Alzheimer’s disease is a step closer to being used to screen older adults.

Detailed standardized guidelines that are needed before a blood test could be used in practice have been published in Alzheimer’s & Dementia. The guidelines establish protocols and reflect the continued efforts of an international working group that includes the University of North Texas Health Science Center.

“If we are ever going to get a blood test for Alzheimer’s disease into the hands of primary care providers, we must have guidelines,” said Sid O’Bryant, PhD, Interim Director of the Institute of Aging and Alzheimer’s Disease Research at UNT Health Science Center.

The highly rigid guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure every lab is following the same procedures when collecting blood, said Dr. O’Bryant, a member of the group and lead author of the paper.

“You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” he said. “You’ll have one lab doing it one way and another lab doing something different.”

Dr. O’Bryant has worked for several years with representatives from across the United States, Australia, Germany, England and other countries to create the standards. Everything from the type of needle used to draw blood to the length of the storage time is specified in the guidelines.

Just as with blood tests for other diseases, such as diabetes, protocols must be established to make sure every lab performs the test exactly the same. Such guidelines are needed before FDA approval can be sought to use the test in a clinical setting.

“For UNTHSC, our next step is to take these blood guidelines and implement them into a clinical trial,” Dr. O’Bryant said. “That’s never been done before.”


Journal Reference:

Christoph Laske, Hamid R. Sohrabi, Shaun M. Frost, Karmele López-de-Ipiña, Peter Garrard, Massimo Buscema, Justin Dauwels, Surjo R. Soekadar, Stephan Mueller, Christoph Linnemann, Stephanie A. Bridenbaugh, Yogesan Kanagasingam, Ralph N. Martins, Sid E. O’Bryant. Innovative diagnostic tools for early detection of Alzheimer’s disease. Alzheimer’s & Dementia, 2015; 11 (5): 561 DOI:10.1016/j.jalz.2014.06.004

© 2015, UNT Health Science Center


New Mechanism for Alzheimer’s Disease Confirmed

(University of Oslo, Faculty of Medicine) Jens Pahnke and his team at the University of Oslo has recently published results in the scientific journal Brain showing that decreased removal of toxic peptides in the brain causes the onset and first clinical signs of Alzheimer’s disease, rather than overproduction as has previously been assumed. This information can now be used to target specific genes to enhance their function in the brain of elderly or people at risk.

World-wide, researchers try to discover the cause for sporadic Alzheimer’s disease which comprises 99% of all Alzheimer’s disease patients. Alzheimer’s patients develop deposits of toxic peptides in the brain that lead to the destruction of the neuronal networks and to clinical signs of disorientation, memory loss, behavioural changes, and finally to death.

By generating a transgene-free mouse model for the more common sporadic form of the disease, the Pahnke team produced results that support the hypothesis of insufficient removal of toxic metabolites in sporadic Alzheimer’s disease. The model animals develop early signs of the disease after 1.5 years of age, precisely at the locations where the first changes appear in Alzheimer’s patients.

Normally, human mutated genes are used to generate animal models of Alzheimer’s disease. Pahnke and his colleagues used a method in which they destructed the function of two genes in the brain that are needed to excrete and digest the toxic Alzheimer’s peptide amyloid-beta. This represents a new model enabling investigations without artificial overexpression of inherited Alzheimer’s disease genes.

The Pahnke lab is internationally known for its discoveries of disturbed export mechanisms in sporadic Alzheimer’s disease. The lab was recently moved to Norway after Jens Pahnke was appointed professor at the University of Oslo’s Faculty of medicine. Pahnke’s team has developed new treatment strategies based on clearance mechanisms at the brains vasculature. These treatments are highly effective in a subset of patients and are used in Germany, Switzerland, Austria, and the USA.

Recent developments of Pahnke and his collaborators aim on medicinal plants that produce ABC transporter-activating agents and can be easily applied as natural medication in patients. These innovative projects are now started in Oslo as the internationally leading centre for research on Alzheimer disease, ABC transporters, and medicinal plants.


Story Source:

The above story is based on materials provided by University of Oslo, Faculty of Medicine. Note: Materials may be edited for content and length.

Journal Reference:

M. Krohn, A. Bracke, Y. Avchalumov, T. Schumacher, J. Hofrichter, K. Paarmann, C. Frohlich, C. Lange, T. Bruning, O. von Bohlen und Halbach, J. Pahnke. Accumulation of murine amyloid-  mimics early Alzheimer’s disease. Brain, 2015; DOI: 10.1093/brain/awv137

University of Oslo, Faculty of Medicine. (2015, May 22). New mechanism for Alzheimer’s disease confirmed. ScienceDaily. Retrieved May 26, 2015 from
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