Posts tagged Alzheimer
Articles and news from the latest research reports.
Drug shows promise in animal model of Alzheimer’s and Parkinson’s with dementia
New research presented in October at the 6th Neurodegenerative Conditions Research and Development Conference in San Francisco demonstrates the role of the investigational compound IRX4204 in alleviating cognitive decline in animal models of Alzheimer’s disease (AD). The presentation entitled “Investigation of the RXR-specific agonist IRX4204 as a Disease Modifying Agent of Alzheimer’s Disease Neuropathology and Cognitive Impairment” was made by lead researcher Giulio Maria Pasinetti, MD, PhD, of the Mount Sinai School of Medicine in New York City.
IRX4204 is a retinoid X receptor (RXR) agonist, meaning it stimulates the retinoid receptor in the brain.The data demonstrates attenuation of AD including prevention of plaque deposits associated with cognitive deterioration in an IRX4204-treated mouse model genetically determined to develop AD. IRX4204 also prevents neuropathological features associated with abnormal tau processing, another form of abnormal protein also found in a form of Parkinson’s disease associated with dementia.
"The treatment of AD remains a serious unmet medical need which IRX4204 may be able to address," Dr. Pasinetti said "Our research show that IRX4204 and other RXR agonists have potential for slowing, and possibly reversing pathology and cognitive deficits in Alzheimer’s disease patients."
Ongoing translational studies in subjects with Alzheimer’s disease and Parkinson’s disease with dementia are currently being developed.
Alzheimer’s disease currently afflicts more than 5 million Americans and may triple in prevalence to more than 16 million Americans by 2050, according to data from The Alzheimer’s Association.
(Source: eurekalert.org)
Biomarkers in Cerebrospinal Fluid Can Identify Patients with Alzheimer´s disease
Analysis of specific biomarkers in a cerebrospinal fluid sample can differentiate patients with Alzheimer’s disease from those with other types of dementia. The method, which is being studied by researchers at Sahlgrenska Academy, may eventually permit earlier detection of Alzheimer’s disease.
Due to the similarity of the symptoms, differentiating patients with Alzheimer’s from those with other types of dementia – or patients with Parkinson disease from those with other motor disorders – is often difficult.
Making a proper diagnosis is essential if proper treatment and medication are to commence at an early stage. A research team at Sahlgrenska Academy, University of Gothenburg, is developing a new method to differentiate patients with Alzheimer’s disease or Parkinson disease by analyzing a cerebrospinal fluid sample.
The study, led by Professor Kaj Blennow and conducted among 450 patients at Skåne University Hospital and Sahlgrenska University Hospital, involved testing five proteins that serve as biomarkers for the two diseases.
“Previous studies have shown that Alzheimer’s disease is associated with biochemical changes in specific proteins of the brain,” says Annika Öhrfelt, a researcher at Sahlgrenska Academy. “This study has found that the inclusion of a new protein can differentiate patients with Alzheimer’s disease from those with Lewy body dementia, Parkinson disease dementia and other types of dementia.”
Similarly, the biomarkers can differentiate patients with Parkinson disease from those with atypical Parkinsonian disorders.
“Additional studies are needed before the biomarkers can be used in clinical practice during the early stages of disease,” says Öhrfelt, “but these results represent an important step along the way.”
(Source: alphagalileo.org)
Clue to Alzheimer’s cause found in brain samples
Researchers at Washington University School of Medicine in St. Louis have found a key difference in the brains of people with Alzheimer’s disease and those who are cognitively normal but still have brain plaques that characterize this type of dementia.
“There is a very interesting group of people whose thinking and memory are normal, even late in life, yet their brains are full of amyloid beta plaques that appear to be identical to what’s seen in Alzheimer’s disease,” says David L. Brody, MD, PhD, associate professor of neurology. “How this can occur is a tantalizing clinical question. It makes it clear that we don’t understand exactly what causes dementia.”
Hard plaques made of a protein called amyloid beta are always present in the brain of a person diagnosed with Alzheimer’s disease, according to Brody. But the simple presence of plaques does not always result in impaired thinking and memory. In other words, the plaques are necessary – but not sufficient – to cause Alzheimer’s dementia.
The new study, available online in Annals of Neurology, still implicates amyloid beta in causing Alzheimer’s dementia, but not necessarily in the form of plaques. Instead, smaller molecules of amyloid beta dissolved in the brain fluid appear more closely correlated with whether a person develops symptoms of dementia. Called amyloid beta “oligomers,” they contain more than a single molecule of amyloid beta but not so many that they form a plaque.
Oligomers floating in brain fluid have long been suspected to have a role in Alzheimer’s disease. But they are difficult to measure. Most methods only detect their presence or absence, or very large quantities. Brody and his colleagues developed a sensitive method to count even small numbers of oligomers in brain fluid and used it to compare amounts in their samples.
The researchers examined samples of brain tissue and fluid from 33 deceased elderly subjects (ages 74 to 107). Ten subjects were normal – no plaques and no dementia. Fourteen had plaques, but no dementia. And nine had a diagnosis of Alzheimer’s disease – both plaques and dementia.
They found that cognitively normal patients with plaques and Alzheimer’s patients both had the same amount of plaque, but the Alzheimer’s patients had much higher oligomer levels.
But even oligomer levels did not completely distinguish the two groups. For example, some people with plaques but without dementia still had oligomers, even in similar quantity to some patients with Alzheimer’s disease. Where the two groups differed completely, according to Brody and his colleagues, was the ratio of oligomers to plaques. They measured more oligomers per plaque in patients with dementia, and fewer oligomers per plaque in the samples from cognitively normal people.
In people with plaques but no dementia, Brody speculates that the plaques could serve as a buffer, binding with free oligomers and keeping them tied down. And in dementia, perhaps the plaques have exceeded their capacity to capture the oligomers, leaving them free to float in the brain’s fluid, where they can damage or interfere with neurons.
Brody cautions that, due to the difficulty in getting samples, oligomer levels have never been measured in living people. Therefore, it’s possible these floating clumps of amyloid beta only form after death. Even so, he says, there is still a clear difference between the two groups.
“The plaques and oligomers appear to be in some kind of equilibrium,” Brody says. “What happens to shift the relationship between the oligomers and plaques? Like much Alzheimer’s research, this study raises more questions than it answers. But it’s an important next piece of the puzzle.”
(Source: news.wustl.edu)
Understanding Alzheimer’s: Study gives insights into how disease kills brain cells
Exactly how Alzheimer’s disease kills brain cells is still somewhat of a mystery, but University of Michigan researchers have uncovered a clue that supports the idea that small proteins prick holes into neurons.
The team also found that a certain size range of clumps of these proteins are particularly toxic to cells, while smaller and larger aggregates of the protein appear to be benign.
The findings, which appear in the journal PLOS ONE, add important detail to the knowledge base regarding this disease that affects 5.4 million Americans in 2012 but remains incurable and largely untreatable. The results could potentially help pharmaceutical researchers target drugs to the right disease mechanisms.
Small proteins called amyloid-beta peptides are the prime suspect for causing cell death in Alzheimer’s. They make up most of the senile plaque fibers found in the brains of autopsied patients. Researchers offer several hypotheses for how the peptides might cause the disease. They blame inflammation, oxidative stress or an imbalance of calcium ions possibly caused by holes in the cell membranes.
The U-M findings strongly support the idea that amyloid peptides damage the membrane around nerve cells and lead to uncontrolled movement of calcium ions into them. Calcium signaling is an important way that cells communicate and healthy cells regulate its flow precisely. The toxic mechanism implicated in the new study could act on its own or together with the other proposed courses and ultimately lead to a loss of brain cells in patients, the researchers say.
Plaque Build-Up in Your Brain May Be More Harmful Than Having Alzheimer’s Gene
A new study shows that having a high amount of beta amyloid or “plaques” in the brain associated with Alzheimer’s disease may cause steeper memory decline in mentally healthy older people than does having the APOE ɛ4 allele, also associated with the disease. The study is published in the October 16, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.
“Our results show that plaques may be a more important factor in determining which people are at greater risk for cognitive impairment or other memory diseases such as Alzheimer’s disease,” said study author Yen Ying Lim, MPsych, with the University of Melbourne in Victoria, Australia. “Unfortunately, testing for the APOE genotype is easier and much less costly than conducting amyloid imaging.”
Image credit: PASIEKA/SCIENCE PHOTO LIBRARY
Doctors took an hour to realise Sarah Merriman had Down’s syndrome after her birth in January 1992. By then, her father, Andy, had phoned friends and family to tell them his wife, Alison, had given birth to a healthy baby. His happy news was dashed. “It was a real shock,” Andy recalls. “From the start, we were warned about the difficulties and troubles that lay ahead for Sarah. Then she was diagnosed as having a hole in her heart. The worry, for the first years of her life, was constant.”
Sarah’s heart healed. She did well at her school in Haringey, north London, and went on to pass the equivalent of four GCSEs. Today, she is studying catering and lives with other students near her college in Somerset. “Sarah is independent and copes with life in a way we could never have imagined just after she was born,” says Andy.
It is a reassuring story, although one major worry still besets the Merriman family: Sarah’s long-term future and her susceptibility to Alzheimer’s disease, a form of dementia that leads to complete loss of memory, speech and awareness and which is closely linked to Down’s syndrome. Among members of the general population, the risk of getting Alzheimer’s before the age of 65 is less than 5%. For a person with Down’s syndrome the figure is 50%.
Could Down’s syndrome point the way to preventing Alzheimer’s disease?
Reducing visual clutter may help Alzheimer’s patients
It’s a finding that could help Alzheimer’s patients better cope with their condition.
Psychologists at the University of Toronto and the Georgia Institute of Technology (Georgia Tech) have shown that the inability to recognize once-familiar faces and objects may have as much to do with difficulty perceiving their distinct features as it does with the capacity to recall from memory.
A study published in the October issue of Hippocampus suggests that memory impairments for people diagnosed with early stage Alzheimer’s disease may in part be due to problems with determining the differences between similar objects.
The research contributes to growing evidence that a part of the brain once believed to support memory exclusively – the medial temporal lobe – also plays a role in object perception.
Prospective Alzheimer’s drug builds new brain cell connections
Washington State University researchers have developed a new drug candidate that dramatically improves the cognitive function of rats with Alzheimer’s-like mental impairment.
Their compound, which is intended to repair brain damage that has already occurred, is a significant departure from current Alzheimer’s treatments, which either slow the process of cell death or inhibit cholinesterase, an enzyme believed to break down a key neurotransmitter involved in learning and memory development.
Such drugs, says Joe Harding, a professor in WSU’s College of Veterinary Medicine, are not designed to restore lost brain function, which can be done by rebuilding connections between nerve cells.
"This is about recovering function,” he says. "That’s what makes these things totally unique. They’re not designed necessarily to stop anything. They’re designed to fix what’s broken. As far as we can see, they work.”
Harding, College of Arts and Sciences Professor Jay Wright and other WSU colleagues report their findings in the online “Fast Forward” section of the Journal of Pharmacology and Experimental Therapeutics.
(Source: news.wsu.edu)
Caffeine may block inflammation linked to mild cognitive impairment
(Image credit: chichacha)
Recent studies have linked caffeine consumption to a reduced risk of Alzheimer’s disease, and a new University of Illinois study may be able to explain how this happens.
“We have discovered a novel signal that activates the brain-based inflammation associated with neurodegenerative diseases, and caffeine appears to block its activity. This discovery may eventually lead to drugs that could reverse or inhibit mild cognitive impairment,” said Gregory Freund, a professor in the U of I’s College of Medicine and a member of the U of I’s Division of Nutritional Sciences.
Freund’s team examined the effects of caffeine on memory formation in two groups of mice—one group given caffeine, the other receiving none. The two groups were then exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow, and then allowed to recover.
The caffeine-treated mice recovered their ability to form a new memory 33 percent faster than the non-caffeine-treated mice. In fact, caffeine had the same anti-inflammatory effect as blocking IL-1 signaling. IL-1 is a critical player in the inflammation associated with many neurodegenerative diseases, he said.
“It’s not surprising that the insult to the brain that the mice experienced would cause learning memory to be impaired. But how does that occur?” he wondered.
The scientists noted that the hypoxic episode triggered the release of adenosine by brain cells.
“Your cells are little powerhouses, and they run on a fuel called ATP that’s made up of molecules of adenosine. When there’s damage to a cell, adenosine is released,” he said.
Just as gasoline leaking out of a tank poses a danger to everything around it, adenosine leaking out of a cell poses a danger to its environment, he noted.
The extracellular adenosine activates the enzyme caspase-1, which triggers production of the cytokine IL-1β, a critical player in inflammation, he said.
“But caffeine blocks all the activity of adenosine and inhibits caspase-1 and the inflammation that comes with it, limiting damage to the brain and protecting it from further injury,” he added.
Caffeine’s ability to block adenosine receptors has been linked to cognitive improvement in certain neurodegenerative diseases and as a protectant against Alzheimer’s disease, he said.
“We feel that our foot is in the door now, and this research may lead to a way to reverse early cognitive impairment in the brain. We already have drugs that target certain adenosine receptors. Our work now is to determine which receptor is the most important and use a specific antagonist to that receptor,” he said.
The study appears in the Journal of Neuroscience and can be viewed online at http://www.jneurosci.org/content/32/40/13945.full
(Source: news.aces.illinois.edu)
The Dementia and Music Project - Chloe Meineck
This project is a culmination of two years research highlighting the advantages of listening to familiar music for dementia sufferers. This coupled with the fact that when many people move into a home they feel lost in their unfamiliar surroundings. The music box, which is all hand made, combines an interactive music player, with a memory box of co-designed special objects.
The film is Barbara talking about her life, her most important objects, music, events and her most treasured people.