Single mild blast exposure can cause brain injuries similar to Alzheimer’s disease

Sep. 24, 2013 — A new study published in the September issue of the Journal of Alzheimer's Disease reports that even a single mild explosion can cause changes in the brain that have similarities to those found in diseases like Alzheimer's disease and chronic traumatic encephalopathy.

Flying debris or getting thrown against other objects are not the only things that make explosions so dangerous. The primary shock waves that emanate from explosions also can kill a person if they are intense enough. However, most blast survivors experience less powerful shock waves that cause less severe immediate symptoms, such as temporary disorientation or headaches, but on the surface leave victims apparently unscathed. Scientists are especially concerned when these mild blast exposures happen repeatedly--likening them to the repetitive hits endured by boxers and other athletes.

"Some of the big questions in mild traumatic brain injury are about a molecule called tau" said Dr. David Cook of VA Puget Sound Health Care System and University of Washington. "In many brain diseases, tau gets chemically modified to create something called 'phospho-tau'. Phospho-tau is important because it is the starting building block of 'tau tangles', which can build up over time and damage brain cells."

The Seattle team used a rodent laboratory model to study brain changes caused by mild blast exposure. Dr. Cook noted, "We were a bit surprised to find that after only a single mild blast, phospho-tau remained elevated for at least a month."

"Tau pathology is part of end-stage TBI," said Dr. Iboja Cernak of the University of Alberta, Canada and a co-author on this report, "so, it is very interesting to discover that persistent phospho-tau increases also appear to be part of earlier phases of blast-induced neurotrauma."

These new findings raise the possibility that early-intervention with tau-based treatments may someday prove valuable in treating blast-induced neurotrauma.

View the original article here

Alzheimer's brain scan advances

18 September 2013 Last updated at 20:29 ETBy James Gallagher Health and science reporter, BBC News

Pioneering brain imaging that can detect the build-up of destructive proteins linked to Alzheimer's has been developed by Japanese scientists.

It could lead to new ways of diagnosing the condition and of testing the effectiveness of new drugs.

The technology, reported in the journal Neuron, can identify inside a living brain clumps of a protein called tau that is closely linked to the disease.

Alzheimer's Research UK said it was promising work.

Alzheimer's disease is a problem for researchers trying to come up with a cure. The brain starts to die years before any symptoms are detected, which means drugs are probably given too late.

A diagnosis of Alzheimer's cannot be made with absolute certainty until a patient has died and their brain is examined. It is also not 100% clear what is the cause of the dementia and what are just symptoms.

One protein, called tau, is very closely linked to the disease, with tangles of tau thought to be one way in which brain cells are killed.

The team, lead by the National Institute of Radiological Sciences in Chiba, used positron emission tomography to build a 3D picture of tau in the brain.

They developed a chemical that could bind to tau and then be detected during a brain scan.

Finding tau in the brain

Tests on mice and people with suspected Alzheimer's showed the technology could detect tau.

Dr Makoto Higuchi, from the National Institute of Radiological Sciences in Japan, said: "Positron emission tomography images of tau accumulation... provide robust information on brain regions developing or at risk for tau-induced neuronal death."

The research is at an early stage, but it could eventually lead to an actual test for Alzheimer's disease.

It might also allow researchers to closely follow the impact drugs that affect tau have on the brain.

Another protein - beta amyloid - is also linked to Alzheimer's and can be detected in similar tests.

Dr Eric Karran, director of research at Alzheimer's Research UK, said: "This promising early study highlights a potential new method for detecting tau - a key player in both Alzheimer's and frontotemporal dementia - in the living brain.

"With new drugs in development designed to target tau, scans capable of visualising the protein inside the brain could be important for assessing whether treatments in clinical trials are hitting their target.

"If this method is shown to be effective, such a scan could also be a useful aid for providing people with an accurate diagnosis, as well as for monitoring disease progression."

View the original article here

Alzheimer's research fraud case set for trial

AppId is over the quota
AppId is over the quota

BOSTON (Reuters) - Two Harvard teaching hospitals and a prominent Alzheimer's disease researcher accused of using falsified data to obtain a government research grant are set to stand trial after a federal appeals court said this week that a lower court erred when it dismissed the case.

The lawsuit accuses Marilyn Albert, a former professor of psychiatry at Harvard Medical School, and Massachusetts General Hospital (MGH), where she was conducting research, of submitting a grant application based on manipulated data.

The data showed results from a trial were scientifically significant when in fact they were not, according to the lawsuit.

Brigham and Women's Hospital, which collaborated on the research, is also a defendant in the case. The lawsuit was brought in 2006 under the False Claims Act, a 150-year-old federal law designed to recover government funds appropriated through fraud.

This is the first time a lawsuit dealing with alleged scientific fraud has been allowed to progress to trial under the False Claims Act, according to Michael Kohn, a lawyer with Kohn, Kohn & Colapinto in Washington, D.C.

Kohn represents the whistle-blower in the case, Kenneth Jones, a former statistician at Massachusetts General Hospital, who filed suit in 2006 claiming the defendants violated the act by including false statements in a $15 million grant application to the National Institutes of Health (NIH).

The case was dismissed in the lower court three days before it was due to go to trial. Barring settlement, a new trial could begin later this year in U.S. District Court in Boston, Kohn said.

If the defendants are found guilty, they could pay as much as $45 million to the U.S. government. By law, whistle-blowers in such cases receive 15 percent to 30 percent of funds recovered.

Albert, who is now director of the Division of Cognitive Neuroscience at Johns Hopkins University School of Medicine, declined to comment except to say in an email: "I am confident that there was no misconduct involved."

Both hospitals said they are confident the researchers acted appropriately and according to the highest standards of scientific integrity.

"While it is disappointing that additional time and resources will have to be devoted to defending the institution and its investigators, the MGH remains confident that the resolution of the case will show that the allegations are without merit," Massachusetts General said in a statement.

Brigham and Women's responded with an identical statement.

INFLUENTIAL RESEARCH

Albert's research was part of an ongoing investigation into the structure of the brain as it progresses toward Alzheimer's disease. She specifically hoped to show that it might be possible to predict, years in advance, who might be destined to develop the disease, based on measurements taken over time of certain regions of the brain.

The results of the trial were published in the scientific journal Annals of Neurology in April 2000 and, according to Jones, proved extremely influential.

"The data appeared to confirm what had been suspected by some very prominent scientists, which is that Alzheimer's disease is associated with decreased blood flow to the brain," Jones said in an interview on Thursday. "The MRIs showed the volume of certain parts of the brain was decreasing in the people who were sick."

There are multiple theories about the cause of Alzheimer's disease.

In March 2001, Jones discovered what he believed to be anomalies in the research, specifically in data produced by one of the researchers, Ronald Killiany. The lawsuit alleges that Killiany revised his initial MRI measurements to prove the hypothesis of the trial.

Killiany, now an associate professor at Boston University School of Medicine, did not return a phone call or email seeking comment. Kohn said he was not named as a defendant. In retrospect, Kohn said, "He probably should have been."

Jones took his concerns to Albert, who authorized an investigation into the matter by Killiany's boss, Mark Moss. She declined to appoint an independent investigator, as requested by Jones, according to the lawsuit.

Moss concluded that Killiany's second set of measurements was more accurate than the initial set. Albert accepted Moss's conclusion and proceeded to apply for an NIH grant in November 2001, according to the lawsuit.

The defense argued before the appeals court that it would not have been unusual or inappropriate for Killiany to re-measure patient brain scans as long as he remained blind to the clinical status of the participants, and that this was a matter for scientific debate.

This argument was accepted when the case was initially heard by the lower court in the United States District Court for the District of Massachusetts. On that basis, it dismissed the case in October 2010. Kohn said the court ruled that scientific fraud could not be brought under the False Claims Act, since the case related to a scientific dispute, not fraud.

The appeals court, however, rejected the argument, saying, "We disagree that the creation of the data in question was necessarily a matter of scientific judgment."

The court noted that the lower court's determination "misses the point that the various results produced in this case were obtained by one scientist purportedly using the same protocol."

The government's Office of Research Integrity declined to say whether it is investigating the case.

Jones said he hopes the trial will shed light on the issue of scientific misconduct.

"My interest is in correcting the science and bringing this academic cheating to light," he said, "and maybe sending a message saying, 'You're being watched, and you shouldn't do it.'"

The case is: U.S. ex rel. Jones v. Brigham and Women's Hospital, et al, 1st U.S. Circuit Court of Appeals, No: 10-2301.

(Editing by Michele Gershberg and Douglas Royalty)