Tau Proteins Very Similar To Prions

Prion Science Still Unfolding

Neurodegenerative disease is the fastest-growing cause of death in the world. Prion disease is responsible for the vast majority of the surge in humans and other mammals.

Professor Goedert, a program leader at the MRC Laboratory of Molecular Biology in Cambridge, believes our best hope of fighting dementia requires predicting who will get neurodegenerative disease and preventing its onset.

His work has just earned him – along with three other neuroscientists – the Brain Prize for 2018 from the Lundbeck Foundation in Denmark. Worth one million euros, it is the most valuable award there is for brain research.

Goedert won the prize for groundbreaking work dating back to the 1980s that was initiated at the LMB by Aaron Klug and Martin Roth and initially involved Claude Wischik, Tony Crowther, Michal Novak, John Walker, Cesar Milstein, Ross Jakes and Maria Grazia Spillantini.

neuroscience and prions

Using human brain tissues, transgenic mice, cultured cells and purified proteins, Professor Goedert demonstrated – despite considerable initial skepticism – the importance of tau protein in Alzheimer’s disease.

“The brains of people who have died of Alzheimer’s disease have two abnormalities – so-called plaques and tangles. These are protein aggregates,” he explains.

Ultimately, these abnormalities kill nerve cells and brain tissue. Plaques are caused by the clumping together of beta-amyloid protein pieces outside nerve cells, which block cell-to-cell signalling. Tangles, meanwhile, are inside the nerve cells and occur when tau protein assembles into clusters of filaments and becomes insoluble. These are the focus of Goedert’s work.

“We all have tau proteins in the brain. Its function is probably to stabilise microtubules inside cells,” he says.

Microtubules are a cellular transport system, like rails, that help material to move in our bodies.

“But it is not a loss of function disease,” Goedert stressed. “It’s a gain of toxic function. The tau protein is one of many proteins that can stabilise these microtubules.

“It looks like if a portion of it turns into these abnormal structures, it’s not sufficient to disrupt this process. The formation of these inclusions is what causes the disease of the cell.”

A pathological pathway leads from the soluble to insoluble filamentous tau.

“Somewhere along it lies the cause of the disease, in the sense of why the nerve cells degenerate and die, which leads to the symptoms of the disease,” explains Goedert.

“Everybody would agree that something on this pathway causes neurodegeneration. Some would argue that there are aggregate species – not the final filaments, but smaller – that have a very active toxic effect.

“I would think it’s equally likely that if you have loads of these filaments inside cells, over a long period of time they are like space-occupying lesions inside a cell body and particularly inside very fine processes.

“They would disrupt all sorts of things inside the cells, including the transport of materials to the periphery, and then at the end the cell dies.

“In the past 10 years, we’ve also found tau proteins exhibit prion-like properties – they can fold in ways that can be transmitted to soluble tau molecules.”

Prions are the misfolded protein equivalent of viral infections and enable a neurodegenerative disease to spread. In the case of Alzheimer’s disease, it means the tau protein aggregates gradually take over.

Prion disease and Alzheimer's disease

“These aggregates form in a small region of the brain and over a long period of time spread to the brain as a whole, and then symptoms appear. Initially, when you have small numbers of these aggregates, there are no symptoms,” adds Goedert.

Much of the group’s work now is focused on the mechanisms behind the spread. Prions migrate, mutate and multiply. There is no species barrier. As such, other mammals are now contracting brain disease from human sewage.

“If we understand more, we might be in a position to prevent the spread from happening and develop compounds that can prevent the symptoms. In addition, you need to be able to predict who is going to get the disease.

“These very early aggregates that form, before the spread occurs, are probably present in people’s brains for decades before the symptoms appear. If you could detect those and predict at an individual level for example that if a person lives another 20 years they are going to get the disease, then you would be in a position to treat that person and prevent the symptoms,” says Professor Goedert, who is an honorary professor of experimental molecular neurology at the University of Cambridge.

“You could give the compounds to everyone over the age of 50. But every treatment has some sort of side effect. Then you would have to treat people who are perfectly healthy.”

No compounds yet exist to deal with the aggregation of tau proteins. And those that have been trialled to tackle amyloid plaques have so far failed.

“One possibility is that the compounds were perfectly good but were given too late,” suggests Prof Goedert. “I think identifying people at risk of developing the disease at a point when they have no symptoms but have some of these pathologies in the brain is really crucial. These are the biomarkers. But until recently it was not possible to detect these things inside living people.”

Studies of the brains of thousands of people have shown that the vast majority have small numbers of these aggregates. Those who had Alzheimer’s disease had many more of them.

“When you see small numbers of aggregates in the brain, you extrapolate that had the person lived for another 20-30 years, they would have got the disease,” says Goedert.

“More recently, it’s become possible to identify aggregates in the brains of living people using PET (positron emission tomography) scanning. You inject mildly radioactive compounds that bind specifically to the aggregates – they don’t see the protein where it’s not aggregated. Then using imaging techniques, you can detect the aggregates.”

PET scans can now be used to detect both beta-amyloid plaques and aggregated tau protein, although the test is not yet sophisticated enough.

“It’s still very early but I think this is going to revolutionise everything,” says Prof Goedert. “In principle you could take a person and image them every year and see whether the pathology progresses. The problem is resolution. Are you going to detect very small numbers of these things? Over time that will improve – but at the moment it’s not there.

“In the long run, it could be like breast cancer screening for women or colonoscopies for men and women. You would take people at the age of 50 and have a PET scan every five or 10 years.”

Current therapies – cholinesterase inhibitors and glutamate receptor antagonists – treat some of the symptoms of Alzheimer’s disease, but do not tackle the underlying biological causes.

These symptoms often begin with memory lapses and gradually progress through to problems with communication, reasoning and orientation. In the latter stages, patients may have difficulties eating or walking, and become increasingly frail and needing help with all aspects of daily life.

prion disease spectrum

“There are so many people working on it now, one can be reasonably optimistic in terms of the timeframe. It’s reasonably clear now what one has to do,” says Prof Goedert.

Understanding the mechanisms of the disease is key – and the work of Professor Goedert and those he shared the prize with is likely to play a critical role in future treatments. Most recently, he has been examining the structure of the tau filaments.

“This lab is very famous for its cryo-electron microscopy technique, which Richard Henderson got a Nobel Prize for last year, and we are collaborating with the group of Sjors Scheres to look at high resolution structures of these tau filaments for Alzheimer’s disease. It tells you how similar or different they are, which I think has a bearing on the prion-like properties of these aggregates,” he said.

Different tau filaments feature in the distinct neurodegenerative diseases such as Pick’s disease and progressive supranuclear palsy, where they form in the absence of beta-amyloid deposits outside brain cells.

Goedert’s recent work in mouse models and in cell cultures suggests filamentous tau clusters propagate through self-seeding (replication, infection and mutation).

“Experimentally, they do. But proving the mechanism takes place in the human brain is difficult. We must interfere with the process and block to prove the theory,” he said. “In the long run, prevention is the thing to do.”

Goedert shares the 2018 Brain Prize with Bart De Strooper (London and Leuven), Christian Haass (Munich) and John Hardy (London) for their groundbreaking research on the genetic and molecular basis of Alzheimer’s disease.

Although he knows them all, Professor Goedert has not collaborated with the others because they all work primarily on beta amyloid plaques.

Unfortunately, prions migrate, mutate and multiply. There is no species barrier. As such, other mammals are now contracting brain disease from human sewage that’s being dumped into our food and water supplies. Sick wildlife and sick livestock are just the tip of the iceberg. Infectious waste isn’t fertilizer for farms, ranches, golf courses, school grounds, parks, gardens or elsewhere. Spreading infectious waste is now spreading brain disease at the speed of light. Preventing brain disease begins with the truth. http://crossbowcommunications.com/wildlife-contracting-brain-disease-from-biosolids/

Alzheimer's disease prevention

Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area of special expertise. Please contact Gary Chandler to join our coalition for reform gary@crossbow1.com

Key Proteins Found In Early Phases Of Alzheimer’s Disease

Tau, Amyloid Detection Could Improve Diagnostic Capabilities

Researchers from Aberdeen have identified changes in the brains of those suffering early signs of Alzheimer’s disease.

A University of Aberdeen study confirmed for the first time that two proteins, assumed to contribute to the disease process, are both present at very early stages of Alzheimer’s disease. Both are present in an area of the brain that is involved in memory formation and information processing–the hippocampus.

Alzheimer's disease and caregivers

The Alzheimer’s Research UK funded the research, which will have implications for the development of new drugs, but may also provide important information for diagnosis of the disease. 

The team, led by Dr Koss and Professor Bettina Platt, used human brain samples provided by the Brains for Dementia Research platform to investigate changes in the brain at different stages of the disease. The researchers developed novel ways to study two proteins (tau and amyloid), both associated with Alzheimer’s disease, and determined how each one contributed to the onset, progression and symptoms of the disease.

“The entire research community is in agreement that it’s important to diagnose Alzheimer’s disease early,” said Dr. Koss. “Our findings will go some way to help achieve this. These early-stage changes in the brains of people with Alzheimer’s disease highlight key biochemical processes that may not only enable improved diagnostic procedures but may also inform drug development.”

Early diagnosis also can help protect caregivers and others from the transmission of Alzheimer’s disease. It’s likely spreading through the bodily fluids of victims. Items exposed, including drinking glasses, utensils are impossible to sterilize.

“There is now real evidence of the potential transmissibility of Alzheimer’s,” says Thomas Wiesniewski M.D. a prion and Alzheimer’s researcher at New York University School of Medicine. “In fact, this ability to transmit an abnormal conformation is probably a universal property of amyloid-forming proteins.”

Prions and Alzheimer's disease

Alzheimer’s Disease Research Report via https://www.eveningexpress.co.uk/fp/news/local/study-identifies-disease-changes/

Visual Test Can Distinguish Alzheimer’s Disease from Normal Aging

Visual Cognition Key To Early Diagnosis

Researchers have developed a new cognitive test that can better determine whether memory impairments are due to very mild Alzheimer’s disease or the normal aging process. The simple test asks subjects to determine if circles containing certain designs match each other, which exercises the hippocampus portion of their brain.

Alzheimer's disease treatment

Memory impairments and other early symptoms of Alzheimer’s are often difficult to differentiate from the effects of normal aging, which makes it hard for doctors to recommend treatment for those affected until the disease has progressed substantially.

Previous studies have shown that a part of the brain called the hippocampus is important to relational memory – the “ability to bind together various items of an event,” said Jim Monti, a University of Illinois postdoctoral research associate who led the work with psychology professor Neal Cohen, who is affiliated with the Beckman Institute at Illinois.

Being able to connect a person’s name with his or her face is one example of relational memory. These two pieces of information are stored in different parts of the brain, but the hippocampus “binds” them so that the next time you see that person, you remember his or her name, Monti said.

Previous research has shown that people with Alzheimer’s disease often have impairments in hippocampal function. So the team designed a task that tested the relational memory abilities of the participants, according to their study report in the journal Neuropsychologia.

Participants were shown a circle divided into three parts, each having a unique design. Similar to the process of name-and-face binding, the hippocampus works to bind these three pieces of the circle together. After the participants studied a circle, they would pick its exact match from a series of 10 circles, presented one at a time.

People with very mild Alzheimer’s disease did worse overall on the task than those in the healthy aging group, who, in turn, did worse than a group of young adults.

The test also revealed an additional memory impairment unique to those with very mild Alzheimer’s disease, indicating the changes in cognition that result from Alzheimer’s are qualitatively different than healthy aging. This unique impairment allows researchers to statistically differentiate between those who did and those who did not have Alzheimer’s more accurately than some of the classical tests used for Alzheimer’s diagnosis, Monti said.“That was illuminating and will serve to inform future work aimed at understanding and detecting the earliest cognitive manifestations of Alzheimer’s disease,” Monti said.

Although this new tool could eventually be used in clinical practice, more studies need to be done to refine the test, he said.

“We’d like to eventually study populations with fewer impairments and bring in neuroimaging techniques to better understand the initial changes in brain and cognition that are due to Alzheimer’s disease,” Monti said.

The Alzheimer’s Association estimates that the number of Americans living with Alzheimer’s disease will increase from 5 million in 2014 to as many as 16 million by 2050.

Source: http://www.seniorjournal.com/NEWS/Alzheimers/2014/20140521_Simple_Visual_Test_Can_Distinguish_Alzheimer’s_Disease_from_Normal_Aging.htm

Early Detection Of Alzheimer’s Disease Improved With Imaging Breakthrough

Early Detection Could Improve Treatment For Alzheimer’s Disease

Using high-resolution functional MRI (fMRI) imaging in patients with Alzheimer’s disease and in mouse models of the disease, Columbia University Medical Center (CUMC) researchers have clarified three fundamental issues about Alzheimer’s disease — where it starts, why it starts there and how it spreads. In addition to advancing understanding of Alzheimer’s, the findings could improve early detection of the disease, when drugs may be most effective. The study was published in the online edition of the journal Nature Neuroscience.

Alzheimer's disease treatment

“It has been known for years that Alzheimer’s starts in a brain region known as the entorhinal cortex,” says co-senior author Scott Small, Boris and Rose Katz Professor of Neurology, professor of radiology, and director of the Alzheimer’s Disease Research Center. “But this study is the first to show in living patients that it begins specifically in the lateral entorhinal cortex, or LEC. The LEC is considered to be a gateway to the hippocampus, which plays a key role in the consolidation of long-term memory, among other functions. If the LEC is affected, other aspects of the hippocampus will also be affected.”

The study also shows that, over time, Alzheimer’s spreads from the LEC directly to other areas of the cerebral cortex, in particular, the parietal cortex, a brain region involved in various functions, including spatial orientation and navigation. The researchers suspect that Alzheimer’s spreads “functionally,” that is, by compromising the function of neurons in the LEC, which then compromises the integrity of neurons in adjoining areas.

A third major finding of the study is that LEC dysfunction occurs when changes in tau and amyloid precursor protein (APP) co-exist. “The LEC is especially vulnerable to Alzheimer’s because it normally accumulates tau, which sensitizes the LEC to the accumulation of APP. Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer’s,” says co-senior author Karen Duff, professor of pathology and cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at CUMC and at the New York State Psychiatric Institute.

In the study, the researchers used a high-resolution variant of fMRI to map metabolic defects in the brains of 96 adults enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP). All of the adults were free of dementia at the time of enrollment.

“Dr. Richard Mayeux’s WHICAP study enables us to follow a large group of healthy elderly individuals, some of whom have gone on to develop Alzheimer’s disease,” says Small. “This study has given us a unique opportunity to image and characterize patients with Alzheimer’s in its earliest, preclinical stage.”

The 96 adults were followed for an average of 3.5 years, at which time 12 individuals were found to have progressed to mild Alzheimer’s disease. An analysis of the baseline fMRI images of those 12 individuals found significant decreases in cerebral blood volume (CBV) — a measure of metabolic activity — in the LEC compared with that of the 84 adults who were free of dementia.

Prions and Alzheimer's disease

A second part of the study addressed the role of tau and APP in LEC dysfunction. While previous studies have suggested that entorhinal cortex dysfunction is associated with both tau and APP abnormalities, it was not known how these proteins interact to drive this dysfunction, particularly in preclinical Alzheimer’s.

To answer this question, explains first author Usman Khan, an MD-PhD student based in small’s lab, the team created three mouse models, one with elevated levels of tau in the LEC, one with elevated levels of APP, and one with elevated levels of both proteins. The researchers found that the LEC dysfunction occurred only in the mice with both tau and APP. The study has implications for both research and treatment.

“Now that we’ve pinpointed where Alzheimer’s starts, and shown that those changes are observable using fMRI, we may be able to detect Alzheimer’s at its earliest preclinical stage, when the disease might be more treatable and before it spreads to other brain regions,” says Small.

In addition, say the researchers, the new imaging method could be used to assess the efficacy of promising Alzheimer’s drugs during the disease’s early stages.

Source: http://www.laboratoryequipment.com/news/2013/12/imaging-answers-where-why-and-how-alzheimers

G8 Dementia Summit Issues Declaration

International Leaders Hold Emergency Meeting On Dementia Epidemic

We, the G8 Health Ministers, met at the G8 Dementia Summit in London on 11 December 2013 to discuss how to shape an effective international response to dementia.
We acknowledge the ongoing work occurring in our countries and globally to identify
dementia as a major disease burden and to address issues related to aging and mental
health, including the World Health Organisation’s 2012 report, Dementia – A Public Health Priority. Building upon the significant research collaborations that exist between our countries and our multilateral partners will strengthen our efforts and allow us to better meet the challenges that dementia presents society.

Alzheimer's disease treatment

We recognize that dementia is not a normal part of aging. It is a condition that impairs the cognitive brain functions of memory, language, perception and thought and which interferes significantly with the ability to maintain the activities of daily living. We also acknowledge that dementia affects more than 35 million people worldwide, a number that is expected to almost double every 20 years.

We note the socio-economic impact of dementia globally. Seventy per cent of the estimated annual world-wide cost of US$604 billion is spent on informal, social and direct medical care. Yet nearly 60 percent of people with dementia live in low and middle income countries so the economic challenge will intensify as life expectancy increases across the globe. These costs are expected to increase significantly if therapies to prevent dementia and improve care and treatment are not developed and implemented. We recognise the need to strengthen efforts to stimulate and harness innovation and to catalyse investment at the global level.

Prions and Alzheimer's disease

Therefore, and in accordance with national, sub-national and local responsibilities, we commit ourselves to:

1. Call for greater innovation to improve the quality of life for people with dementia and their carers while reducing emotional and financial burden. We therefore welcome the UK’s decision to appoint a global Dementia Innovation Envoy to draw together international expertise to stimulate innovation and to co-ordinate international efforts to attract new sources of finance, including exploring the possibility of developing a private and philanthropic fund to support global dementia innovation;

2. The ambition to identify a cure or a disease-modifying therapy for dementia by 2025 and to increase collectively and significantly the amount of funding for dementia research to reach that goal. We will report biennially on expenditure on publicly funded national
dementia research and related research infrastructure; and we will increase the number
of people in dementia related research studies;

3. Work together, share information about the research we fund, and identify strategic priority areas, including sharing initiatives for big data, for collaboration and cooperation;

4. Develop a co-ordinated international research action plan which accounts for the current state of the science, identifies gaps and opportunities, and lays out a plan for working together to address them;
5. Encourage open access, where possible to all publicly funded dementia research and to
make the research data and results available for further research as quickly as possible,
while protecting the privacy of individuals and respecting the political and legal
frameworks of the countries in which the research is conducted;
6. Take stock of our current national incentive structure for research, working in partnership with the Organisation for Economic Co-operation and Development (OECD), and consider what changes could be made to promote and accelerate discovery and
research and its transformation into innovative and efficient care and services;
7. Hold a series of high-level fora throughout 2014, in partnership with the OECD, WHO,
the European Commission, the EU Joint Programme on Neurodegenerative Disease
(JPND), and civil society, to develop cross sector partnerships and innovation,
focused on:
• Social impact investment – UK-led
• New care and prevention models – Japan-led
• Academia-industry partnerships – Canada and France co-led
8. Call upon the WHO and OECD to identify dementia as an increasing threat to global
health and support countries to strengthen health and social care systems to improve
care and services for people with dementia;
9. Call upon the UN Independent Expert on the enjoyment of all human rights by older
persons to integrate the perspective of older people affected by dementia into their work;
10. Call upon all sectors to treat people affected by dementia with dignity and respect, and to enhance their contribution to dementia prevention, care and treatment where they can; and
11. Call upon civil society to continue and to enhance global efforts to reduce stigma,
exclusion and fear.
12. We will meet again in the United States in February 2015 with other global experts,
including WHO and OECD, to review the progress that has been made on our research
agenda.

Source/More: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/265869/2901668_G8_DementiaSummitDeclaration_acc.pdf

Dementia Researchers Ask To Make Epidemic Immediate Priority

Neurodegenerative Diseases Spreading Fast

The suffering and costs of dementia would be reduced by preventative measures if the Group of Eight nations adopt a model that has worked in fighting heart disease, a group of doctors and scientists said. The unstoppable epidemic already has 44 million people in it’s grasp and its spreading rapidly.

Alzheimer's disease treatment

“About half of Alzheimer’s disease cases worldwide might be attributable to known risk factors,” they said in a statement before a G-8 meeting in London tomorrow to coordinate responses to the condition. “Taking immediate action on the known risk factors could perhaps prevent up to one-fifth of predicted new cases by 2025.”

The costs of dementia were estimated at $604 billion for 2010, the group said, and the number of cases is set to more than triple by 2050. The 111 signatories from 36 countries called on governments to back more research into prevention, and policies such as promotion of healthier diets. The G-8 are the U.K., U.S., Germany, France, Canada, Italy, Russia and Japan.

“The choice is stark,” said Zaven Khachaturian, a signatory and editor-in-chief of U.S. journalAlzheimer’s & Dementia. “Either you invest money in creating this infrastructure for preventing or delaying dementia, or continue along the way. If we continue with the current trends, no country’s health-care system will be able to provide care.”

caregivers Alzheimer's disease

50 Million People Already Have Dementia

Alzheimer’s Disease International estimates that 44 million people worldwide have dementia, which will rise to 76 million in 2030 and 135 million by 2050, according to data from the group of Alzheimer’s associations.

About $40 billion has been invested in drug development efforts that haven’t produced effective new medicines, the researchers said in today’s statement. Even so, recent research suggests there may be cheap options to help tackle the problem.

A cocktail of vitamins B6 and B12 and folic acid would cost pennies a day and slowed atrophy of gray matter in brain areas affected by Alzheimer’s disease, according to a study published in May by the Proceedings of the National Academy of Sciences.

About half the fall in deaths from conditions such as heart disease and stroke in the past 50 years resulted from modifying risk factors, according to the scientists advocating prevention. Taking a similar approach to dementia by encouraging middle-aged people to adopt healthy lifestyles may ward off the condition as it does other diseases and save “huge sums,” they said.

treat Alzheimer's disease

Healthy Lifestyle, Diet Helps Avert Alzheimer’s Disease

A healthy lifestyle includes exercising; not smoking; following a diet rich in fruit, vegetables and fish; avoiding obesity, diabetes and excessive alcohol; and treating high blood pressure, the researchers said.

Other research is helping to identify people at risk. A person’s chance of getting dementia before age 65 may develop as early as adolescence, according to a study that suggests teens with high blood pressure or who drink excessively are at risk.

Other risk factors include stroke, use of antipsychotics, father’s dementia, drug intoxication, as well as short stature and low cognitive function, according to the study of Swedish men published by the journal JAMA Internal Medicine in August.

G-8 governments should set goals, stimulate more collaborative research, coordinate policies and establish consistent rules for data sharing, intellectual property and ethics, Khachaturian said in a telephone interview.

The U.S. Food and Drug Administration hasn’t cleared new drugs for memory loss conditions in a decade. Approved medicines such as Eisai Co. (4523)’s Aricept ease symptoms without slowing or curing dementia.

Alzheimer's disease research

A joint U.S.-European Union task force in 2011 found that all disease-modifying treatments for Alzheimer’s in the previous decade failed late-stage trials “despite enormous financial and scientific efforts.” Since then, at least four more experimental treatments have failed.

Eric Karran, director of research at the charity Alzheimer’s Research UK, who wasn’t among the signatories to the statement, said that failed trials can provide useful lessons. One of the four medicines, Eli Lilly & Co. (LLY)’s solanezumab, is undergoing further tests to determine if it helps people with mild Alzheimer’s disease, Karran said.

“If we could just get efficacy in one approach, we will unlock so much else, we will get so much more understanding,” Karran said at a press conference on Dec. 4. “If solanezumab is shown to work in mild Alzheimer’s disease, the pathway will be to take that earlier and earlier.”

Source: http://www.bloomberg.com/news/2013-12-10/dementia-researchers-call-for-g-8-to-focus-on-prevention.html

Alzheimer’s Disease Could Sink Global Economies

Neurodegenerative Disease Rising Globally

John Kauwe, assistant professor of biology and neuroscience at Brigham Young University, delivered a sobering presentation about the myths of Alzheimer’s disease at Weber Human Services on Friday afternoon. The talk, hosted by the Utah chapter of the Alzheimer’s Association, stressed the dire need for funding of Alzheimer’s disease research as more individuals near the ages of Alzheimer’s susceptibility.

Alzheimer's disease treatment

“There have been articles that have come out recently saying quite clearly that Alzheimer’s is the most expensive disease that our country is dealing with right now,” Kauwe said. “It is the largest financial burden on our country as far as diseases go. On top of that, Alzheimer’s disease is the only one of the top ten causes of death in the United States with no prevention and no cure.

“Our country will buckle under the weight of caring for the people who are suffering from this disease. Government officials are starting to see that it’s in their financial interest to put the money in now and alleviate the problem. It’s something we need to deal with sooner rather than later.”

Kauwe said Alzheimer’s disease is a combination of genetics, lifestyle and environment, and as such, there is no way to prevent or slow down the disease by diet and exercise alone.

“The idea that there are specific dietary practices or supplements that will stop or slow down or prevent Alzheimer’s disease is a really appealing one,” Kauwe said. “Unfortunately, while those are all good things to do and you should eat your vegetables and you should take healthy supplements and you should manage your diet properly, there’s no compelling evidence that that will stop or prevent or delay Alzheimer’s disease. If the possibility of reducing the risk for Alzheimer’s motivates you to eat healthier and stay active, great; it’s just not clear that that’s going to solve this problem completely.”

treat Alzheimer's disease

Kauwe likened the process of genetic expression to baking a cake. Your DNA is like your cookbook. Your  RNA is like the paper on which you write the recipe from your cookbook on so you don’t have to lug the  book into the kitchen. And you have the proteins the RNA acts upon, which is essentially the “baking” process – the process of implementing your genetic code in your body. During the baking process your cake can be affected by things like altitude or forgetting the salt. The expression of your genetic code can also be affected during the “baking process” by things like your environment, your diet and your life experiences.

“Everything, every chemical you’re ever exposed to, even the way you act with your family, your religion, your government — they all interact with your genes to create you,” Kauwe said, noting that children who experience the early death of their mothers, before the age of 10 or 12, actually have higher risk of Alzheimer’s.

In addition to the myth that diet alone can prevent Alzheimer’s, Kauwe said that contrary to popular belief, Alzheimer’s is fatal, there are no treatments for the disease, and the discovery of new genes associated with Alzheimer’s does not signal an imminent cure.

“New genes provide info that can be used to better inform our quest to cure the disease. In six short years, we went from one gene for late-onset Alzheimer’s disease, to 20 genes for late-onset Alzheimer’s disease,” Kauwe said. “The progress we’ve made in the past five or six years is amazing. Especially when you consider that it took us 20 years to find the second gene. One of the challenges is we may have the gene, but we don’t know why it affects the risk of Alzheimer’s.”

Prions and Alzheimer's disease

According to Kauwe, such knowledge can only be attained with more funding. He believes that if Alzheimer’s research drew the kind of funding that breast cancer and HIV do, “we would have prevention avenues and treatment avenues that are at least equivalent to those two diseases.”

When asked if he felt his presentation was discouraging for his audience, Kauwe said he thought it was, but that’s no reason to ignore reality.

“It is discouraging. It’s discouraging for me, too,” Kauwe said. “But we need to know that work has to be done. We can’t sit there and pretend that it’s going to be cured when it’s not. We have to face that reality.The idea is that for people to understand that there is no simple solution and that there’s a purpose to the research that myself and my colleagues are conducting. We know that the reality is there’s no simple solution; we’re motivated to find one.”

Kauwe said that though the obstacle Alzheimer’s presents may be discouraging, there are ways for people to fight back. He encouraged people to become advocates for dealing with the disease, to take steps to maximize the quality of their lives, to donate their time and money, and to participate in research efforts such as clinical trials.

“Elderly, non-demented individuals are the ideal people for those control groups; the older the better,” Kauwe said. “If you’re very old and very cognitively sharp and healthy, then you’re an ideal candidate for genetics studies that need to compare your DNA to those of the individuals who are affected by Alzheimer’s disease. It doesn’t take much. The clinical trials and genetics studies that they can participate in are carefully designed, they’re carefully regulated, their privacy is protected and their safety is protected and they shouldn’t have any concerns about participating.”

Kate Nederostek, director of programs for the Utah Chapter of the Alzheimer’s Association, said her organization runs a support group for those who have been recently diagnosed with Alzheimer’s and are still in the early stages of the disease.

“Our support group consists of early-stage individuals. They come together, support one another, learn from one another. Many of them have become advocates for us,” Nederostek said. “They’ll visit local representatives and as travel to D.C. with us to talk with Congress to let them know of their affiliation with the association, their affliction, what their future holds, and to ask and demand for additional support for Alzheimer’s disease. The quicker we find a cure or an effective treatment for this disease process, the more lives are going to be affected and we’re going to reduce the cost that this disease has on our nation.”

Source: http://www.standard.net/stories/2013/11/09/sobering-future-fight-against-alzheimers

Alzheimer’s Epidemic Escalating In Most Countries

Numerous Causes Triggering Neurodegenerative Disease

A new government-funded report confirms what advocacy groups have been warning for years: The number of people in the USA with Alzheimer’s disease will almost triple by 2050, straining the health care system and taxing the health of caregivers.

Numbers are projected to rise from about 5 million now to 13.8 million. The disease robs people of their memory, erases personality and makes even routine tasks like dressing and bathing impossible.

Alzheimers epidemic

“We’re going to need coordinated efforts for this upcoming epidemic,” says lead author Jennifer Weuve, assistant professor of medicine at Rush Institute for Healthy Aging in Chicago. “People have trouble getting their heads around these numbers, but imagine if everyone in the state of Illinois (population 12.8 million) had Alzheimer’s disease. I look around Chicago and can’t imagine it.”

The study is published Wednesday in the journal Neurology. Researchers analyzed information from 10,802 black and white Chicago residents, ages 65 and older, from 1993 to 2011. Participants were interviewed and assessed for dementia every three years. Age, race and level of education were factored into the research. The projections are similar to a study done 10 years ago but include new data from the 2010 Census about death rates and future population rates. An upcoming study will examine the effect on health care costs, which are expected to exceed $2 trillion, according to the Alzheimer’s Association.

“These numbers are more credible because they involve new Census data,” says Dallas Anderson, director of population studies and epidemiology of Alzheimer’s disease at the National Institute on Aging. “If you know anyone who has Alzheimer’s disease now, you know how dire this projection is for the nation.”

The three-fold increase is largely the result of the aging Baby Boomers, born between 1946 and 1964. The main risk for Alzheimer’s is age. The population of people 65 and older is expected to more than double from 40.3 million to 88.5 million, according to the 2010 Census.

“We’ve had great success in this country when we’ve decided to focus on a condition,” Weuve says. “We’ve done it with good research in heart disease, cancer and HIV, but we are in our infancy when it comes to Alzheimer’s research.”

Alzheimer’s is the only disease among the top six killers in the USA for which there is no prevention, cure or treatment. The government boosted funding last year and made prevention a 2025 goal. Funding for the disease was $606 million — exceeding $500 million for the first time in 2012. But it trails other diseases: HIV at $3 billion and cancer at $6 billion. An additional $100 million for Alzheimer’s research for 2013 is awaiting approval, the Alzheimer’s Association says.

Alzheimer's disease research

“We need to put the pedal to the metal on research,” says George Vradenburg, chairman of USAgainst Alzheimer’s, an advocacy group. “We need to find a way to prevent this terrible disease.”

Former president RonaldReagan, who left office in 1989, disclosed in 1994 that he had Alzheimer’s. Others include Robert Sargent Shriver, actress Rita Hayworth and singer Glen Campbell. In 2011, the University of Tennessee’s legendary women’s basketball coach Pat Summitt revealed she has Alzheimer’s.

The study was financed by the National Institute on Aging, National Institutes of Health and the Alzheimer’s Association.

“There is great urgency for meaningful, timely and comprehensive action,” says Maria Carrillo, vice president of medical and scientific relations for the Alzheimer’s Association.

Source: http://www.usatoday.com/story/news/nation/2013/02/06/alzheimers-dementia-epidemic-numbers-to-triple/1881151/ 

Neurodegenerative Diseases Closely Related

Alzheimer’s Part Of Deadly TSE Family

It’s not clear how the tangles of the protein tau commonly seen in people with Alzheimer’s disease spread throughout the brain in the course of disease—and to a modest extent in ordinary aging. But European researchers recently described an experiment in transgenic mice in which extracts containing tau tangles appeared to induce the formation and spread of new tangles in otherwise healthy mouse brains.

The findings seem most immediately relevant to Alzheimer’s disease and are consistent with other evidence suggesting that “once the tau pathway has started, for whatever reason, it probably becomes self-sustaining,” says Michel Goedert, a neuroscientist at Cambridge University who helped to lead the study, published online June 7 in Nature Cell Biology.

Alzheimer's disease research

Most Alzheimer’s disease researchers had been targeting the buildup of beta-amyloid, a sequence of amino acids that form plaques in the brains of people with the disease. But experimental anti-amyloid drugs have shown little or no effect in stemming the disease in people, even where there is evidence that they have cleared amyloid from the brain.

Many researchers now believe that in people who already have symptoms, tau is the major driver of disease [see Targeting Amyloid in Alzheimer’s Disease: No Longer Enough?]. They are looking to the tau pathway as a major target for potential anti-Alzheimer’s therapies.

“You could argue that it would be a perfect therapeutic target really, because it probably would prevent the symptoms of the disease from ever appearing,” says Goedert.

In the new study, Goedert and colleagues took brain extracts from P301S transgenic mice, whose brain cells make the mutant form of human tau found in inherited frontotemporal dementia and develop tangles as a result. After confirming that these extracts contained P301S tau, the researchers injected the material into the brains of ALZ17 mice, a transgenic strain that makes normal human forms of tau and ordinarily does not develop tangles.

The quantity of tangles injected was too small to be detected with a standard staining technique a day later, but 6, 12 and 15 months later, the ALZ17 mice showed abundant evidence of tangles. Tests showed that these tangles had been formed out of the mice’s own, human-type tau, not the mutant P301S tau, indicating that they had been induced (and that the mutant form didn’t just reproduce). The tau tangles also had spread to neighboring brain regions in a manner similar to the spread of tangles in people with Alzheimer’s disease.

treat Alzheimer's disease

In control experiments, neither ALZ17 mice injected with non-tau extracts nor those injected with brain extracts from ordinary “wild-type” mice showed any tau pathology. Moreover, when the researchers used antibodies to remove the P301S tau from the extracts, then injected them into the new mice, they found that this tau-free extract failed to induce tangles in the ALZ17 mice—thus strengthening the case that P301S tau was the active, tangle-inducing agent in the extracts.

These results raise several issues. For example, the tangles induced in ALZ17 mice did not seem to cause brain damage or behavioral changes the way they do in people with Alzheimer’s and other tau-associated diseases, at least not during the 15 months after injection.

“What this means, at present, we don’t know,” says Goedert. But he adds that it may have to do with the inherent limitations of mouse models, including the fact that mouse brains on the whole seem much less prone to human neurodegenerative disease. Transgenic disease-model mice typically are designed to make (express) an unusually large number of copies of disease-causing genes, often pathologically mutated ones, and “if you don’t overexpress,” Goedert says, “you normally don’t get pathology within the lifespan of the mouse.”

A second key question is whether other forms of tau could also induce this infection-like spreading. Goedert and his colleagues are experimenting with injections of tangle-containing extracts from human brains with Alzheimer’s, as well as brain extracts from other tau-associated neurodegenerative diseases including Pick’s disease and progressive supranuclear palsy.

Neuroscientist Marc Diamond’s lab at the University of California, San Francisco, already has shown in laboratory experiments that tau can form into functionally distinct aggregates (clumps), thus perhaps accounting for the variety of diseases with which tau aggregates have been associated. In another study, published May 8 in the Journal of Biological Chemistry, the Diamond lab showed that aggregates of misfolded tau can be taken up by cells, causing internal tau to clump and then to be re-emitted to “infect” neighboring cells.

Both Diamond and Goedert suspect that this transmission mechanism is similar to that seen in prion diseases such as Creutzfeld-Jakob disease. But because tau aggregates are much less hardy than prions, they are unlikely to be as easily transmitted. However, the same misfolding and spreading process may apply to other neurodegenerative diseases, and not just those featuring prions or tau.

Parkinson’s disease and dementia with Lewy bodies, for example, have been associated with the spread of a misfolded protein called alpha-synuclein. While alpha-synuclein-expressing transgenic mice so far are “not as useful” as tau-expressing mice, Goedert says, he hopes soon to inject such mice with brain extracts from people with Parkinson’s disease to see if the extracts cause the spread of alpha-synuclein pathology. Other researchers already have shown that in cell transplant experiments in people with Parkinson’s, alpha-synuclein pathology seems to spread from the diseased host brain to the transplanted, previously healthy cells.

“I think this is going to be a very important area of research,” Diamond says, “because there are going to be more general [not just disease-specific] mechanisms that allow aggregates to move around and corrupt proteins, and if you can target these mechanisms, then potentially you could get silver bullets for neurodegenerative disease”

Source: http://www.dana.org/news/features/detail.aspx?id=22840