brain disease


Study: New Antibody Therapy Can Reverse Traumatic Brain Injury Damage (In Mice)

Cleveland Browns QB Jason Campbell lies near midfield after suffering a concussion in a game on Nov. 24, 2013. Traumatic brain injuries, whether they occur on a sports field or in a war zone, are on the rise. (David Richard/AP)

Cleveland Browns QB Jason Campbell lies near midfield after suffering a concussion in a game on Nov. 24, 2013. Traumatic brain injuries, whether they occur on a sports field or in a war zone, are on the rise. (David Richard/AP)

Traumatic brain injuries, whether they occur on a sports field or in a war zone, are on the rise.

What’s worse, these head traumas have been linked to long-term neurodegenerative diseases, notably Alzheimer’s and a condition known as chronic traumatic encephalopathy, or CTE.

Now, a team of researchers report they’ve discovered the “missing link” between traumatic brain injuries and these degenerative brain diseases and developed a special antibody that may help prevent the conditions — at least in mice.

In a study published online in the journal Nature, researchers at Beth Israel Deaconess Medical Center identify the “missing link” culprit as “cis P-tau, a misshapen and toxic species of tau protein that has not been previously identified,” says Kun Ping Lu, MD, PhD, the study’s co-senior author and chief of the Division of Translational Therapeutics in the Department of Medicine at BIDMC and professor of medicine at Harvard Medical School.

Lu, in an interview, explains how these toxic proteins can build up in the brain and start causing serious damage after repeated head injuries:

A single concussion, a mild traumatic brain injury (TBI), results in moderate induction of cis P-tau, which returns to the baseline within 2 weeks. However, repetitive concussions, as might occur in contact sports, result in robust induction of cis P-tau that is persistent for months in mouse brains. This is similar to what is produced following a single severe TBI caused by a blast, as seen in military blast, or an impact, as seen in a severe car accident. Strikingly, cis P-tau is produced as soon as 12 hours after TBI, setting in motion the destructive course of events that leads to Alzheimer’s and CTE.

cis P-tau protein is extremely neurotoxic, disrupting neuron structure and function, progressively spreading to other neurons throughout the brain over time, leading to neuron death. Therefore, cis P-tau has the ability to kill one neuron after another in the brain over time, eventually leading to Alzheimer’s and CTE. These results in animal models are consistent with clinical observations that either repetitive concussions or single severe TBI can lead to Alzheimer’s or CTE.

Importantly, our cis antibody is not only able to spot only the toxic cis P-tau, but also to neutralize its toxicity to neurons. As a result, treating TBI mice with cis antibody can stop brain damage after TBI and prevent its debilitating long-term consequence of Alzheimer’s and CTE. Thus, cis P-tau is an early driver of TBI and its related Alzheimer’s disease and CTE, which can be effectively blocked by antibody therapy.

The immediate implications of these findings are to emphasize TBI prevention; however, if concussion occurs, it is critically important to allow the body defense system to remove the toxic tau protein completely before another concussion occurs. The most exciting development will be to humanize our current monoclonal antibody to develop early intervention to treat TBI and to prevent Alzheimer’s disease and CTE, which can be done within next a few years. In addition, because the same toxic tau protein also destroys brain cells in Alzheimer’s, this early intervention may be used to treat this most common form of dementia in older individuals.

The BIDMC release also states that “Lu and Zhou have interests in Pinteon Therapeutics, Inc., which has licensed Pin 1 technology from BIDMC.” Continue reading

Why To Exercise Today: Avoid Brain Shrinkage As You Age



Middle-age adults take note: the exercise you shirk today may lead to shrunken brain tissue in a couple of decades.

This, according to research presented at the American Heart Association Epidemiology/Lifestyle meeting in Baltimore this week.

After reviewing exercise data taken from more than 1,200 adults who were around 40 years old — a subset of the Framingham Heart Study — researchers found that twenty years later when these same individuals underwent MRI scans, those with “lower fitness levels in midlife also had lower brain tissue levels in later life,” said Nicole L. Spartano, Ph.D., lead author and a postdoctoral fellow at the Boston University School of Medicine.

Though the findings are preliminary, Spartano says it looks like there’s a link between lower fitness levels and faster brain aging. Since the MRI’s in this study were done on people about 58 years old, the researchers didn’t expect to see high rates of dementia, but they did detect “the beginning of shrinkage,” Spartano said. “We look at the brain MRI as an early warning sign for deterioration. This may give us some idea of decreased cognition a decade or so later.”

Specifically, the researchers evaluated fitness based on how the heart changes in the early stages of exercise. Continue reading

A Boxer’s Brain And The Evolution Of Sports-Related Head Injuries

(don's athletics/Flickr)

(don’s athletics/Flickr)

(This post originally appeared on Boston University’s Research News website as “Head Examiner: Neurologist Ann McKee Talks About Battered Brains, Tangled Tau, And The Future of Sports“)

By Barbara Moran

For Ann McKee, every brain tells a story. And sometimes it’s a tragic one. McKee, a professor of neurology and pathology at the Boston University School of Medicine (MED), is the director of neuropathology for the Veterans Affairs New England Healthcare System, and also directs BU’s Chronic Traumatic Encephalopathy Center. Chronic traumatic encephalopathy (CTE) is a degenerative brain disease found in athletes with a history of repetitive brain trauma. McKee first identified its telltale mark—tiny tangles of a protein called tau, clustered around blood vessels—in the dissected brain of a boxer who had been diagnosed with Alzheimer’s disease.

Although most people associate CTE with professional football players, McKee has found it in the brains of soccer, hockey, rugby, and baseball players as well. Her research has alerted the public to the long-term dangers of repetitive hits in sports and raised tough questions about safety. McKee was invited to speak about this growing public health concern at the annual meeting of the American Association for the Advancement of Science (AAAS), the world’s largest general scientific society, held in February 2015 in San Jose, CA. She told BU Research the story behind her discovery of CTE, and what it might mean for the future of sports.

BU Research: You’re a world expert on tau protein, which has been implicated in Alzheimer’s, CTE, and other brain diseases. Have you studied tau your whole career?

McKee: Yes. I love tau.


It’s beautiful, the way it collects throughout the nervous system and just sort of fills up the nerve cell. It’s always been quite lovely to look at, visually captivating. I mean, how crazy is that? But it’s true.

When you started studying tau, you were studying Alzheimer’s?

I was interested in Alzheimer’s, but I also worked on PSP (progressive supernuclear palsy), and something called corticobasal degeneration.

Those are not so famous.

No, they’re not so famous. But I got very involved in defining what these individual diseases looked like. It’s like being at the Smithsonian and being really interested in one collection of pottery or something. And once you start understanding it, you start seeing all these differences, and it’s like “Whoa!”

Brains with CTE show a distinct pattern of tau protein, seen here in brown. The two slides on the bottom come from the brain of a 66-year-old ex-NFL player. The slides on top are from a 65-year-old man without CTE. Photo courtesy of Ann McKee

Do you remember the first time you saw a brain with CTE?

Yes. It was phenomenally interesting. The first case was Paul Pender, a professional [middleweight] boxer here in the Boston area. He had twice been world champion. That was my first time seeing it under the microscope. I looked at the slide and it was like “Oh my God! This is so amazing. I’ve never seen anything like this.” It just blew my mind. That was 2003.

How did it look different than, say, a brain with Alzheimer’s?

Alzheimer’s disease has these beta amyloid plaques that look like small puffs of smoke throughout the brain. Continue reading

‘Moon Shot To The Mind:’ First Steps Toward Curing Brain Diseases

Let the historical record reflect: Last week in Boston, a cadre of some of the most powerful scientists and politicians in America declared war on brain disease.

They likened their new campaign to President Kennedy’s famous speech exactly 50 years earlier declaring his ambition to send an American to the moon. Will last week’s One Mind For Research conference prove as noteworthy a launch?

Perhaps. What worries me is that the War on Cancer seems a more apt analogy than the moon program: A broad coalition of people with a deep personal investment in beating a disease commit to pouring resources and energy into the cause. (The “One Mind” Website is here, including a 10-year plan.) But the War on Cancer has been running for decades now, and some call its results underwhelming.

I asked California businessman Garen Staglin, who is spearheading the brain initiative along with retired Rep. Patrick Kennedy, where it goes from here. And frankly, I was also entreating him to overcome my skepticism and help me believe that the brain will be as conquerable as the moon. His answers, lightly edited:

Q: You gathered leaders from Vice President Joe Biden to NIH director Frances Collins at the One Mind For Research conference in Boston. You showed you could get important people into a room together. Now what?

We’re on two tracks:

In the middle of July we’re convening a conference of CEOs of pharmaceutical companies, foundations, technology people and others to sign up for a new public-private partnership that will actually be part of a new way of governing and managing neuroscience across all aspects.

We have commenced a search for our executive director, interviewing candidates around the world.

All of the scientific advisory board have committed to stay with the process. We have also commenced a working group to develop the networked Web methodologies to allow this plan to be transparent, visible and available on the Web in a working environment.

On the Website, we’re going to develop a patient registry for people to sign up and donate tissue. We hope to develop at least 1 million samples and a similar number of genome surveys. We also want people to register if they’re willing to be part of clinical trials on a disease- or non-specific basis.

And we’ll begin to develop the actual campaign itself, testing messages and doing public fundraising to begin to achieve our goal of philanthropy at a level that starts to mirror what’s going on in cancer, heart disease and AIDS.

You say the Obama administration supports your initiative. What does that mean?

Ultimately I think that means we’ll work toward either some form of mandated inter-agency cooperation from the White House up to and including a potential executive order. Continue reading