Posts tagged alzheimer's disease
Articles and news from the latest research reports.
(Image caption: This is a coronal view of the hippocampus brain region of a patient with Alzheimer’s disease. Image courtesy of Daniel Tranel’s Laboratory at the UI’s Department of Neurology.)
Alzheimer’s patients can still feel the emotion long after the memories have vanished
A new University of Iowa study further supports an inescapable message: caregivers have a profound influence—good or bad—on the emotional state of individuals with Alzheimer’s disease. Patients may not remember a recent visit by a loved one or having been neglected by staff at a nursing home, but those actions can have a lasting impact on how they feel.
The findings of this study are published in the September 2014 issue of the journal Cognitive and Behavioral Neurology.
UI researchers showed individuals with Alzheimer’s disease clips of sad and happy movies. The patients experienced sustained states of sadness and happiness despite not being able to remember the movies.
“This confirms that the emotional life of an Alzheimer’s patient is alive and well,” says lead author Edmarie Guzmán-Vélez, a doctoral student in clinical psychology, a Dean’s Graduate Research Fellow, and a National Science Foundation Graduate Research Fellow.
Guzmán-Vélez conducted the study with Daniel Tranel, UI professor of neurology and psychology, and Justin Feinstein, assistant professor at the University of Tulsa and the Laureate Institute for Brain Research.
Tranel and Feinstein published a paper in 2010 that predicted the importance of attending to the emotional needs of people with Alzheimer’s, which is expected to affect as many as 16 million people in the United States by 2050 and cost an estimated $1.2 trillion.
“It’s extremely important to see data that support our previous prediction,” Tranel says. “Edmarie’s research has immediate implications for how we treat patients and how we teach caregivers.”
Despite the considerable amount of research aimed at finding new treatments for Alzheimer’s, no drug has succeeded at either preventing or substantially influencing the disease’s progression. Against this foreboding backdrop, the results of this study highlight the need to develop new caregiving techniques aimed at improving the well-being and minimizing the suffering for the millions of individuals afflicted with Alzheimer’s.
For this behavioral study, Guzmán-Vélez and her colleagues invited 17 patients with Alzheimer’s disease and 17 healthy comparison participants to view 20 minutes of sad and then happy movies. These movie clips triggered the expected emotion: sorrow and tears during the sad films and laughter during the happy ones.
About five minutes after watching the movies, the researchers gave participants a memory test to see if they could recall what they had just seen. As expected, the patients with Alzheimer’s disease retained significantly less information about both the sad and happy films than the healthy people. In fact, four patients were unable to recall any factual information about the films, and one patient didn’t even remember watching any movies.
Before and after seeing the films, participants answered questions to gauge their feelings. Patients with Alzheimer’s disease reported elevated levels of either sadness or happiness for up to 30 minutes after viewing the films despite having little or no recollection of the movies.
Quite strikingly, the less the patients remembered about the films, the longer their sadness lasted. While sadness tended to last a little longer than happiness, both emotions far outlasted the memory of the films.
The fact that forgotten events can continue to exert a profound influence on a patient’s emotional life highlights the need for caregivers to avoid causing negative feelings and to try to induce positive feelings.
“Our findings should empower caregivers by showing them that their actions toward patients really do matter,” Guzmán-Vélez says. “Frequent visits and social interactions, exercise, music, dance, jokes, and serving patients their favorite foods are all simple things that can have a lasting emotional impact on a patient’s quality of life and subjective well-being.”
Down syndrome helps researchers understand Alzheimer’s disease
The link between a protein typically associated with Alzheimer’s disease and its impact on memory and cognition may not be as clear as once thought, according to a new study from the University of Wisconsin-Madison’s Waisman Center. The findings are revealing more information about the earliest stages of the neurodegenerative disease.
The researchers — including lead study author Sigan Hartley, UW-Madison assistant professor of human development and family studies, and Brad Christian, UW-Madison associate professor of medical physics and psychiatry and director of PET Physics in the Waisman Laboratory for Brain Imaging and Behavior — looked at the role of the brain protein amyloid-β in adults living with Down syndrome, a genetic condition that leaves people more susceptible to developing Alzheimer’s. They published their findings in the September issue of the journal Brain.
"Our hope is to better understand the role of this protein in memory and cognitive function," says Hartley. "With this information we hope to better understand the earliest stages in the development of this disease and gain information to guide prevention and treatment efforts."
However, the findings of their study not only may help scientists better understand the condition as it impacts those living with Down syndrome, but they are also relevant to adults without the genetic syndrome.
"There are many unanswered questions about at what point amyloid-β, together with other brain changes, begins to take a toll on memory and cognition and why certain individuals may be more resistant than others," says Hartley.
The UW-Madison scientists, along with collaborators at the University of Pittsburgh, studied 63 healthy adults with Down syndrome, aged 30 to 53, who did not exhibit clinical signs of Alzheimer’s or other forms of dementia. They found that many adults with Down syndrome had high levels of amyloid-β protein but did not suffer the expected negative consequences of the elevated protein.
Alzheimer’s disease is the sixth leading cause of death in the U.S. People with Down syndrome are born with an extra copy of the 21st chromosome, where the gene that codes for the amyloid-β protein resides.
For the study, which was conducted over the course of two days, researchers used magnetic resonance imaging (MRI) and positron emission tomography (PET) scans to capture images of the participants’ brains. Twenty-two of the 63 participants had elevated levels of amyloid-β but showed no evidence of diminished memory or cognitive function when compared to those without elevated levels of the protein. The researchers controlled for differences in age and intellectual level.
Similarly, when assessed as a continuous measure, amyloid-β levels were not tied to differences in memory or cognitive ability, such as changes in visual and verbal memory, attention and language.
(Source: news.wisc.edu)
Researchers Reveal Pathway that Contributes to Alzheimer’s Disease
Researchers at Jacksonville’s campus of Mayo Clinic have discovered a defect in a key cell-signaling pathway they say contributes to both overproduction of toxic protein in the brains of Alzheimer’s disease patients as well as loss of communication between neurons — both significant contributors to this type of dementia.
Their study, in the online issue of Neuron, offers the potential that targeting this specific defect with drugs “may rejuvenate or rescue this pathway,” says the study’s lead investigator, Guojun Bu, Ph.D., a neuroscientist at Mayo Clinic, Jacksonville, Fla.
“This defect is likely not the sole contributor to development of Alzheimer’s disease, but our findings suggest it is very important, and could be therapeutically targeted to possibly prevent Alzheimer’s or treat early disease,” he says.
The pathway, Wnt signaling, is known to play a critical role in cell survival, embryonic development and synaptic activity — the electrical and chemical signals necessary for learning and memory. Any imbalance in this pathway (too much or too little activity) leads to disease — the overgrowth of cells in cancer is one example of overactivation of this pathway.
While much research on Wnt has focused on diseases involved in overactive Wnt signaling, Dr. Bu’s team is one of the first to demonstrate the link between suppressed Wnt signaling and Alzheimer’s disease.
“Our finding makes sense, because researchers have long known that patients with cancer are at reduced risk of developing Alzheimer’s disease, and vice versa,” Dr. Bu says. “What wasn’t known is that Wnt signaling was involved in that dichotomy.”
Using a new mouse model, the investigators discovered the key defect that leads to suppressed Wnt signaling in Alzheimer’s. They found that the low-density lipoprotein receptor-related protein 6 (LRP6) is deficient, and that LRP6 regulates both production of amyloid beta, the protein that builds up in the brains of AD patients, and communication between neurons. That means lower than normal levels of LRP6 leads to a toxic buildup of amyloid and impairs the ability of neurons to talk to each other.
Mice without LRP6 had impaired Wnt signaling, cognitive impairment, neuroinflammation and excess amyloid.
The researchers validated their findings by examining postmortem brain tissue from Alzheimer’s patients — they found that LRP6 levels were deficient and Wnt signaling was severely compromised in the human brain they examined.
The good news is that specific inhibitors of this pathway are already being tested for cancer treatment. “Of course, we don’t want to inhibit Wnt in people with Alzheimer’s or at risk for the disease, but it may be possible to use the science invested in inhibiting Wnt to figure out how to boost activity in the pathway,” Dr. Bu says.
“Identifying small molecule compounds to restore LRP6 and the Wnt pathway, without inducing side effects, may help prevent or treat Alzheimer’s disease,” he says. “This is a really exciting new strategy — a new and fresh approach.”
Simple test can help detect Alzheimer’s before dementia signs show
York University researchers say a simple test that combines thinking and movement can help to detect heightened risk for developing Alzheimer’s disease in a person, even before there are any telltale behavioural signs of dementia.
Faculty of Health Professor Lauren Sergio and PhD candidate Kara Hawkins who led the study asked the participants to complete four increasingly demanding visual-spatial and cognitive-motor tasks, on dual screen laptop computers. The test aimed at detecting the tendency for Alzheimer’s in those who were having cognitive difficulty even though they were not showing outward signs of the disease.
“We included a task which involved moving a computer mouse in the opposite direction of a visual target on the screen, requiring the person’s brain to think before and during their hand movements,” says Sergio in the School of Kinesiology & Health Science. “This is where we found the most pronounced difference between those with mild cognitive impairment (MCI) and family history group and the two control groups.”
Hawkins adds, “We know that really well-learned, stereotyped motor behaviours are preserved until very late in Alzheimer’s disease.” These include routine movements, such as walking. The disruption in communication will be evident when movements require the person to think about what it is they are trying to do.
For the test, the participants were divided into three groups – those diagnosed with MCI or had a family history of Alzheimer’s disease, and two control groups, young adults and older adults, without a family history of the disease.
The study, Visuomotor Impairments in Older Adults at Increased Alzheimer’s Disease Risk, published in the Journal of Alzheimer’s Disease, found that 81.8 per cent of the participants that had a family history of Alzheimer’s disease and those with MCI displayed difficulties on the most cognitively demanding visual motor task.
“The brain’s ability to take in visual and sensory information and transform that into physical movements requires communication between the parietal area at the back of the brain and the frontal regions,” explains Sergio. “The impairments observed in the participants at increased risk of Alzheimer’s disease may reflect inherent brain alteration or early neuropathology, which is disrupting reciprocal brain communication between hippocampal, parietal and frontal brain regions.”
“In terms of being able to categorize the low Alzheimer’s disease risk and the high Alzheimer’s disease risk, we were able to do that quite well using these kinematic measures,” says Hawkins. “This group had slower reaction time and movement time, as well as less accuracy and precision in their movements.”
Hawkins says the findings don’t predict who will develop Alzheimer’s disease, but they do show there is something different in the brains of most of the participants diagnosed with MCI or who had a family history of the disease.
World Alzheimer Report 2014: Evidence for dementia risk reduction
The World Alzheimer Report 2014 ‘Dementia and Risk Reduction: An analysis of protective and modifiable factors’, released today, calls for dementia to be integrated into both global and national public health programmes alongside other major non communicable diseases (NCDs).
Alzheimer’s Disease International (ADI) commissioned a team of researchers, led by Professor Martin Prince from King’s College London, to produce the report. ADI is publishing this report, in conjunction with World Alzheimer’s Day (21 September) and as a part of World Alzheimer’s Month, an international campaign to raise awareness and challenge stigma.
The report reveals that control of diabetes and high blood pressure as well as measures to encourage smoking cessation and to reduce cardiovascular risk, have the potential to reduce the risk of dementia even in late-life. The report found that diabetes can increase the risk of dementia by 50%. Obesity and lack of physical activity are important risk factors for diabetes and hypertension, and should, therefore, also be targeted.
While cardiovascular health is improving in many high income countries, many low and middle income countries show a recent pattern of increasing exposure to cardiovascular risk factors, with rising rates of diabetes, heart disease and stroke.
Smoking cessation is strongly linked in the report with a reduction in dementia risk. For example, studies of dementia incidence among people aged 65 years and over show that ex-smokers have a similar risk to those who have never smoked, while those who continue to smoke are at much higher risk.
Furthermore, the study revealed that those who have had better educational opportunities have a lower risk of dementia in late-life. Evidence suggests that education has no impact on the brain changes that lead to dementia, but reduces their impact on intellectual functioning.
The evidence in the report suggest that if we enter old age with better developed, healthier brains we are likely to live longer, happier and more independent lives, with a much reduced chance of developing dementia. Brain health promotion is important across the life span, but particularly in mid-life, as changes in the brain can begin decades before symptoms appear.
The report also urges NCD programs to be more inclusive of older people, with the message that it’s never too late to make a change, as the future course of the global dementia epidemic is likely to depend crucially upon the success or failure of efforts to improve global public health, across the population. Combining efforts to tackle the increasing global burden of NCDs will be strategically important, efficient and cost effective. Leading a healthier lifestyle is a positive step towards preventing a range of long-term diseases, including cancer, heart disease, stroke and diabetes.
However, survey data released by Bupa* has shown that many people are unclear about the causes and actions they can take to potentially reduce their risk of dementia. Just over a sixth (17%) of people realised that social interaction with friends and family could impact on the risk. Only a quarter (25%) identified being overweight as a possible factor, and only one in five (23%) said physical activity could affect the risk of developing dementia and losing their memories. The survey also revealed that over two thirds (68%) of people surveyed around the world are concerned about getting dementia in later life.
Professor Martin Prince, from King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and author of the report, commented: “There is already evidence from several studies that the incidence of dementia may be falling in high income countries, linked to improvements in education and cardiovascular health. We need to do all we can to accentuate these trends. With a global cost of over US$ 600 billion, the stakes could hardly be higher.”
Marc Wortmann, Executive Director, Alzheimer’s Disease International said: “From a public health perspective, it is important to note that most of the risk factors for dementia overlap with those for the other major non communicable diseases (NCDs). In high income countries, there is an increased focus on healthier lifestyles, but this is not always the case with lower and middle income countries. By 2050, we estimate that 71% of people living with dementia will live in these regions, so implementing effective public health campaigns may help to reduce the global risk.”
Professor Graham Stokes, Global Director of Dementia Care, Bupa, said: “While age and genetics are part of the disease’s risk factors, not smoking, eating more healthily, getting some exercise, and having a good education, coupled with challenging your brain to ensure it is kept active, can all play a part in minimising your chances of developing dementia. People who already have dementia, or signs of it, can also do these things, which may help to slow the progression of the disease.”
* These figures, unless otherwise stated, are from YouGov Plc. Total sample size was 8,513, from the UK (2,401), Australia (1,000), Chile (1,000), China (1,031), Poland (1,002), and Spain (1,077). Fieldwork was undertaken online, between 17–25 July 2014. The figures have been weighted and are representative of all adults (aged 18+) in each country. An even weighting was applied to each country to find a ‘Global Average’.
(Image caption: Shown are fMRI scans across all subjects in the study. The yellow and red areas in Section A represent parts of the brain that are activated while subjects are forming “gist memories” of pictures viewed. Section B represents areas of increased activation, shown in yellow and red, as detailed memories are being formed. Credit: Image courtesy of Jagust Lab)
Researchers find neural compensation in people with Alzheimer’s-related protein
The human brain is capable of a neural workaround that compensates for the buildup of beta-amyloid, a destructive protein associated with Alzheimer’s disease, according to a new study led by UC Berkeley researchers.
The findings, published today (Sunday, Sept. 14) in the journal Nature Neuroscience, could help explain how some older adults with beta-amyloid deposits in their brain retain normal cognitive function while others develop dementia.
“This study provides evidence that there is plasticity or compensation ability in the aging brain that appears to be beneficial, even in the face of beta-amyloid accumulation,” said study principal investigator Dr. William Jagust, a professor with joint appointments at UC Berkeley’s Helen Wills Neuroscience Institute, the School of Public Health and Lawrence Berkeley National Laboratory.
Previous studies have shown a link between increased brain activity and beta-amyloid deposits, but it was unclear whether the activity was tied to better mental performance.
The study included 22 healthy young adults and 49 older adults who had no signs of mental decline. Brain scans showed that 16 of the older subjects had beta-amyloid deposits, while the remaining 55 adults did not.
The researchers used functional magnetic resonance imaging (fMRI) to track the brain activity of subjects in the process of memorizing pictures of various scenes. Afterwards, the researchers tested the subjects’ “gist memory” by asking them to confirm whether a written description of a scene – such as a boy doing a handstand – corresponded to a picture previously viewed. Subjects were then asked to confirm whether specific written details of a scene – such as the color of the boy’s shirt – were true.
“Generally, the groups performed equally well in the tasks, but it turned out that for people with beta-amyloid deposits in the brain, the more detailed and complex their memory, the more brain activity there was,” said Jagust. “It seems that their brain has found a way to compensate for the presence of the proteins associated with Alzheimer’s.”
What remains unclear, said Jagust, is why some people with beta-amyloid deposits are better at using different parts of their brain than others. Previous studies suggest that people who engage in mentally stimulating activities throughout their lives have lower levels of beta-amyloid.
“I think it’s very possible that people who spend a lifetime involved in cognitively stimulating activity have brains that are better able to adapt to potential damage,” said Jagust.
Study Finds Air Pollution Harmful to Young Brains
Pollution in many cities threatens the brain development in children.
Findings by University of Montana Professor Dr. Lilian Calderón-Garcidueñas, MA, MD, Ph.D., and her team of researchers reveal that children living in megacities are at increased risk for brain inflammation and neurodegenerative changes, including Alzheimer’s or Parkinson’s disease.
Calderón-Garcidueñas’ findings are detailed in a paper titled “Air pollution and children: Neural and tight junction antibodies and combustion metals, the role of barrier breakdown and brain immunity in neurodegeneration,” which can be found online at http://iospress.metapress.com/content/xx6582688105j48h/.
The study found when air particulate matter and their components such as metals are inhaled or swallowed, they pass through damaged barriers, including respiratory, gastrointestinal and the blood-brain barriers and can result in long-lasting harmful effects.
Calderón-Garcidueñas and her team compared 58 serum and cerebrospinal fluid samples from a control group living in a low-pollution city and matched them by age, gender, socioeconomic status, education and education levels achieved by their parents to 81 children living in Mexico City.
The results found that the children living in Mexico City had significantly higher serum and cerebrospinal fluid levels of autoantibodies against key tight-junction and neural proteins, as well as combustion-related metals.
“We asked why a clinically healthy kid is making autoantibodies against their own brain components,” Calderón-Garcidueñas said. “That is indicative of damage to barriers that keep antigens and neurotoxins away from the brain. Brain autoantibodies are one of the features in the brains of people who have neuroinflammatory diseases like multiple sclerosis.”
The issue is important and relevant for one reason, she explained. The breakdown of the blood-brain barrier and the presence of autoantibodies to important brain proteins will contribute to the neuroinflammation observed in urban children and raises the question of what role air pollution plays in a 400 percent increase of MS cases in Mexico City, making it one of the main diagnoses for neurology referrals.
Calderón-Garcidueñas points out that there is a need for a longitudinal follow-up study to determine if there is a relationship between the cognition deficits and brain MRI alterations previously reported in Mexico City children, and their autoimmune responses. But what is clear is that the kids are suffering from immune dysregulation.
Once there is a breakdown in the blood-brain barrier, not only will particulate matter enter the body but it also opens the door to harmful neurotoxins, bacteria and viruses.
“The barriers are there for a reason,” she explains. “They are there to protect you, but once they are broken the expected results are not good.”
The results of constant exposure to air pollution and the constant damage to all barriers eventually result in significant consequences later in life. She explains that the autoimmune responses are potentially contributing to the neuroinflammatory and Alzheimer’s and Parkinson’s pathology they are observing in young urban children.
While the study focused on children living in Mexico City, others living in cities where there are alarming levels of air pollution such as Los Angeles, Philadelphia-Wilmington, New York City, Salt Lake City, Chicago, Tokyo, Mumbai, New Delhi or Shanghai, among others, also face major health risks. In the U.S. alone, 200 million people live in areas where pollutants such as ozone and fine particulate matter exceed the standards.
“Investing in defining the central nervous system pathology associated with exposure to air pollutants in children is of pressing importance for public health,” Calderón-Garcidueñas said.
The full article is scheduled to be published in Volume 43, Issue 3 of the Journal of Alzheimer’s Disease and will appear online at http://www.j-alz.com in December with a 2015 copyright.
(Source: news.umt.edu)
![New Molecular Target is Key to Enhanced Brain Plasticity
As Alzheimer’s disease progresses, it kills brain cells mainly in the hippocampus and cortex, leading to impairments in “neuroplasticity,” the mechanism that affects learning, memory, and thinking. Targeting these areas of the brain, scientists hope to stop or slow the decline in brain plasticity, providing a novel way to treat Alzheimer’s. Groundbreaking new research has discovered a new way to preserve the flexibility and resilience of the brain.
The study, led by Tel Aviv University’s Prof. Illana Gozes and published in Molecular Psychiatry, reveals a nerve cell protective molecular target that is essential for brain plasticity. According to Prof. Gozes, “This discovery offers the world a new target for drug design and an understanding of mechanisms of cognitive enhancement.”
Prof. Gozes is the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and director of the Adams Super Center for Brain Studies at the Sackler Faculty of Medicine and a member of TAU’s Sagol School of Neuroscience. Also contributing to the study were Dr. Saar Oz, Oxana Kapitansky, Yanina Ivashco-Pachima, Anna Malishkevich, Dr. Joel Hirsch, Dr. Rina Rosin-Arbersfeld, and their students, all from TAU. TAU staff scientists Dr. Eliezer Gildai and Dr. Leonid Mittelman provided the state-of-the-art molecular cloning and cellular protein imaging necessary for the study.
Building on past breakthroughs
The new finding is based on Prof. Gozes’ discovery of NAP, a snippet of a protein essential for brain formation (activity-dependent neuroprotective protein [ADNP]). As a result of this discovery, a drug candidate that showed efficacy in mild cognitive impairment patients, a precursor to Alzheimer’s disease, is being developed. NAP protects the brain by stabilizing microtubules — tiny cellular cylinders that provide “railways and scaffolding systems” to move biological material within cells and provide a cellular skeleton. Microtubules are of particular importance to nerve cells, which have long processes and would otherwise collapse. In neurodegenerative diseases like Alzheimer’s, the microtubule network falls apart, hindering cellular communication and cognitive function.
"Clinical studies have shown that Davunetide (NAP) protects memory in patients suffering from mild cognitive impairment preceding Alzheimer’s disease," said Prof. Gozes. "While the mechanism was understood in broad terms, the precise molecular target remained a mystery for years. Now, in light of our new research, we know why and we know how to proceed."
Stabilizing microtubules
The breakthrough was the discovery of the mechanism promoting microtubule growth at the tips of the tubes (“rails”). The researchers found that the NAP structure allows it to bind to the tip of the growing microtubule, the emerging “railway,” through specific microtubule end-binding proteins, which adhere to microtubules a bit like locomotors to provide for growth and forward movement, while the other end of the microtubule may to be disintegrating. These growing tips enlist regulatory proteins that are essential for providing plasticity at the nerve cell connection points, the synapses.
"We have now revealed that ADNP through its NAP motif binds the microtubule end binding proteins and enhances nerve cell plasticity, providing for brain resilience. We then discovered that NAP further enhances ADNP microtubule binding," said Prof. Gozes.
Researchers hope their discovery will help move Davunetide (NAP) and related compounds into further clinical trials, increasing the potential of future clinical use. Prof. Gozes is continuing to investigate microtubule end-binding proteins to better understand their protective properties in the brain.](http://40.media.tumblr.com/9d2bba78cb2facc524e3c70b810ac967/tumblr_nbp01pnFr91rog5d1o1_500.png)
New Molecular Target is Key to Enhanced Brain Plasticity
As Alzheimer’s disease progresses, it kills brain cells mainly in the hippocampus and cortex, leading to impairments in “neuroplasticity,” the mechanism that affects learning, memory, and thinking. Targeting these areas of the brain, scientists hope to stop or slow the decline in brain plasticity, providing a novel way to treat Alzheimer’s. Groundbreaking new research has discovered a new way to preserve the flexibility and resilience of the brain.
The study, led by Tel Aviv University’s Prof. Illana Gozes and published in Molecular Psychiatry, reveals a nerve cell protective molecular target that is essential for brain plasticity. According to Prof. Gozes, “This discovery offers the world a new target for drug design and an understanding of mechanisms of cognitive enhancement.”
Prof. Gozes is the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and director of the Adams Super Center for Brain Studies at the Sackler Faculty of Medicine and a member of TAU’s Sagol School of Neuroscience. Also contributing to the study were Dr. Saar Oz, Oxana Kapitansky, Yanina Ivashco-Pachima, Anna Malishkevich, Dr. Joel Hirsch, Dr. Rina Rosin-Arbersfeld, and their students, all from TAU. TAU staff scientists Dr. Eliezer Gildai and Dr. Leonid Mittelman provided the state-of-the-art molecular cloning and cellular protein imaging necessary for the study.
Building on past breakthroughs
The new finding is based on Prof. Gozes’ discovery of NAP, a snippet of a protein essential for brain formation (activity-dependent neuroprotective protein [ADNP]). As a result of this discovery, a drug candidate that showed efficacy in mild cognitive impairment patients, a precursor to Alzheimer’s disease, is being developed. NAP protects the brain by stabilizing microtubules — tiny cellular cylinders that provide “railways and scaffolding systems” to move biological material within cells and provide a cellular skeleton. Microtubules are of particular importance to nerve cells, which have long processes and would otherwise collapse. In neurodegenerative diseases like Alzheimer’s, the microtubule network falls apart, hindering cellular communication and cognitive function.
"Clinical studies have shown that Davunetide (NAP) protects memory in patients suffering from mild cognitive impairment preceding Alzheimer’s disease," said Prof. Gozes. "While the mechanism was understood in broad terms, the precise molecular target remained a mystery for years. Now, in light of our new research, we know why and we know how to proceed."
Stabilizing microtubules
The breakthrough was the discovery of the mechanism promoting microtubule growth at the tips of the tubes (“rails”). The researchers found that the NAP structure allows it to bind to the tip of the growing microtubule, the emerging “railway,” through specific microtubule end-binding proteins, which adhere to microtubules a bit like locomotors to provide for growth and forward movement, while the other end of the microtubule may to be disintegrating. These growing tips enlist regulatory proteins that are essential for providing plasticity at the nerve cell connection points, the synapses.
"We have now revealed that ADNP through its NAP motif binds the microtubule end binding proteins and enhances nerve cell plasticity, providing for brain resilience. We then discovered that NAP further enhances ADNP microtubule binding," said Prof. Gozes.
Researchers hope their discovery will help move Davunetide (NAP) and related compounds into further clinical trials, increasing the potential of future clinical use. Prof. Gozes is continuing to investigate microtubule end-binding proteins to better understand their protective properties in the brain.
New technique could benefit Alzheimer’s diagnosis
Swinburne researchers have developed a technique to create a highly sensitive surface for measuring the concentration of a peptide that is a biomarker for early stage Alzheimer’s disease.
(Image caption: Ultrashort-laser pulses were used to write ripples on the surface of sapphire. The self-organised nano-structure of ripples (seen in the image) is a perfect sensing surface after coating with a nanometre-thin layer of gold made by evaporation or sputtering. Such surface ripples were used in the study of amyloid detection.)
Alzheimer’s disease was first recorded more than 100 years ago, but there is still no effective therapy to stop or slow the progression of the disease. Sufferers can lose up to 60 per cent of their neuronal cells before a diagnosis is obtained.
Diagnosis at the very early stages before neuronal degeneration has begun is vital for testing and developing new treatments.
Abnormality of the beta amyloid peptide in cerebrospinal fluid appears to be the earliest and most significant marker of Alzheimer’s. Currently there are no standardised tests to detect these biomarkers.
The researchers have developed a sensor based on nanotechnology that outperforms commercial sensors and demonstrates fast and reliable measurement of beta amyloid oligomers at low concentrations.
The key to the high sensitivity is the laser nano-textured gold coated surface. This sensor can identify concentrations of beta amyloid in a quantitative manner for the first time.
“We showed that sensors based on light scattering can indeed deliver QUANTATIVE measurements and they can be made fast,” Professor of Nanophotonics Saulius Juodkazis said.
“The sensor platform we developed by laser nano-texturing of surfaces is delivering results of the highest sensitivity and repeatability.
“The challenge is to create fast and efficient fabrication of sensors based on nanotechnology and develop new analytical methods of detection. This means we should be able to detect markers of diseases at far lower levels.”
Surface enhanced Raman spectroscopy (SERS) is one of the most sensitive and highly specific label-free detection methods which may evolve as a detection technique for different forms of beta amyloid or as a rapid, low cost technique to validate new biomarkers before developing standard assays for enzyme-linked immunosorbent assays (ELISAs).
This research is a PhD project work of Dr Ricardas Buividas who received his doctorate in May 2014. It was published in the Journal of Biophotonics.
(Source: swinburne.edu.au)
The effects of very early Alzheimer’s disease on the characteristics of writing by a renowned author
Iris Murdoch (I.M.) was among the most celebrated British writers of the post-war era. Her final novel, however, received a less than enthusiastic critical response on its publication in 1995. Not long afterwards, I.M. began to show signs of insidious cognitive decline, and received a diagnosis of Alzheimer’s disease, which was confirmed histologically after her death in 1999. Anecdotal evidence, as well as the natural history of the condition, would suggest that the changes of Alzheimer’s disease were already established in I.M. while she was writing her final work. The end product was unlikely, however, to have been influenced by the compensatory use of dictionaries or thesauri, let alone by later editorial interference. These facts present a unique opportunity to examine the effects of the early stages of Alzheimer’s disease on spontaneous written output from an individual with exceptional expertise in this area. Techniques of automated textual analysis were used to obtain detailed comparisons among three of her novels: her first published work, a work written during the prime of her creative life and the final novel. Whilst there were few disparities at the levels of overall structure and syntax, measures of lexical diversity and the lexical characteristics of these three texts varied markedly and in a consistent fashion. This unique set of findings is discussed in the context of the debate as to whether syntax and semantics decline separately or in parallel in patients with Alzheimer’s disease.