The Tau Protein and the Future of Alzheimer's Research

Dr. Claude Wischik, Alzheimer's Researcher
Claude Wischik_3
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Dr. Claude Wischik, a renowned 63-year-old researcher who's spent the last 30 years immersed in the fight against Alzheimer's disease, wants to change the current focus of Alzheimer's research.

As the Wall Street Journal recently noted, he isn't afraid of stirring controversy to do it, either. He's dared to imply that, when it comes to the focus of what he estimates to be $15 billion spent worldwide on Alzheimer's disease in the last few years, the emperor has no clothes. Or more to the point of his focus, the emperor has been wearing the wrong clothes.

Why does Wischik disagree with some of his most-funded Alzheimer's research colleagues?

In a nutshell, much of the argument comes down to proteins. Wischik believes that the tau protein -- which can best be described as twisted brain fibers, or "tangles," found in Alzheimer's patients -- are the central culprit. As Wischik notes, this is not a new theory. Tau proteins were an early focus of the disease until, in the last few decades, much of the scientific community diverted attention and dollars to a focus on beta amyloid proteins, which create sticky plaque in the brain and, as Wischik believes, are a red herring in the Alzheimer's battle.

The rising debate over these two proteins is certainly an important new development in Alzheimer's research. But Wischik is controversial for another reason, too. Currently, he wears two hats, as scientist and cofounder of TauRx Pharmaceuticals, Ltd., which has developed an experimental Alzheimer's drug currently awaiting critically important clinical trials. It's important to note that he stands to gain financially from this shift in research priorities.

As a young PhD student at Cambridge University in the 1980s, what got you motivated to study Alzheimer's? I know that after finishing medical school in 1980, you went to Cambridge to study for your PhD under Professor Sir Martin Roth.

Dr. Claude Wischik: Yes, I studied under a very eminent person in Cambridge -- Sir Martin. I had no personal involvement in the disease. But Sir Martin was already making major contributions to research in Alzheimer's disease by providing the first evidence that the tangle pathology originally discovered by Alzheimer was highly correlated with clinical dementia.

For our readers, can you explain in layman's terms the difference between Alzheimer's and dementia?

CW: Dementia describes a broad syndrome of loss of mental capacity. It stems from what people thought of as senile psychosis and takes two forms: Two-thirds is true Alzheimer's and one-third is vascular. There are two dimensions to the diagnosis:

  1. Cognitive decline can be defined by mini test -- you can quantify if you have dementia.
  2. Pathology dimension, which measures quantity and spread of tangled proteins.

If you look up Alzheimer 's disease in DSM IV, there's:

  1. A set of criteria, including a loss of functioning to interfere with professional and life activities.
  2. Documented defects in memory, judgment, language, and mathematical abilities.
  3. There's no other cause.

Is Alzheimer's hereditary?

CW: The genetic component is estimated to be between 10 and 15 percent. For the other 85 percent, there's no genetic link.

I know there are many theories in various camps about the causes and potential cures of Alzheimer's. Set the record straight for us. What is your theory for how it's caused and how it can best be treated?

CW: Refocus on the tau protein is important. Out of the ashes of failure has come the fact that more attention needs to be focused on the tau side of the research, and that's really happening now. Companies and researchers are picking it up. As recently as 2007, it was tough because you were going against the mainstream.

I am focusing my work on what is, in fact, the original direction of Alzheimer's research. Sir Martin had already come to the conclusion that amyloid blocks don't explain dementia. You can have a lot of amyloid buildup in the brain and not be demented. Even if you reduce the amount of amyloid, you aren't likely to be less demented. But amyloid theory has prevailed. One of the common phrases has been, "If it ain't amyloid, it ain't Alzheimer's disease."

What new scientific developments are bringing hope to the field of Alzheimer's research?

CW: At a practical level, tools are being developed to help speed the diagnosis, which is important because people have this pathology in their brains for many years before it's detected. These include:

  1. Great strides with imaging and integration of brain imaging into clinical care.
  2. Interesting work with biological markers, like blood and cerebral spinal fluid-based ones.
  3. Brain-wave analysis. We want to optimize psychometric tools for use at a very basic and widespread general-practitioner level to measure brain disconnection.

Outside of scientific development, what else is coming that may raise new hopes for the roughly 36 million people worldwide afflicted with Alzheimer's or dementia?

CW: One big cause for hope is that Alzheimer's is the focus of an intense worldwide enterprise. There are, of course, different schools of thought. But the great thing is that there's a lot of work being done by many capable people.

With the WHO estimating 7.7 million new cases of dementia every year, and with 66 million new cases expected by the year 2030, how will the world be able to manage this disease? It's a terrifying statistic.

CW: I think through education and new diagnostic technologies, as well as treatments and new service paradigms, so that general practitioners have confidence and tools to convert into diagnosis and action. Today, it costs, on average, $7,000 to provide a full workup with scans, physician's time, and blood tests. This is just not workable on a mass scale.

What advice do you have for caregivers in the midst of caring for someone with Alzheimer's? According to the Alzheimer's Association, in 2012, 15.4 million caregivers provided more than 17.5 billion hours of unpaid care valued at $216 billion.

CW: Assert your rights. Go to your general practitioner, and if he or she is not helpful, find another one. Insist on being seen by a neurologist. Quick, easy, and affordable tests are not available today, but soon we will be able to diagnose early and get people into the right treatments.

Also, sort out finances and care and relief that will be necessary for the, often, one person tasked with such a heavy caregiving burden.

I can't help but think that, for the many caregivers who'll read this article, they must be looking at the Alzheimer's patients and/or family members for whom they're caring and wondering, "Am I next?" They are likely worried for themselves and curious about what proactive steps they should take to prevent the disease. What is your concept of "run, don't walk" (attending to care immediately) and why should caregivers pay attention to it?

CW: Early diagnosis is important. But that requires breaking down barriers and fighting stigmas. A whole dynamic occurs in the gradual journey between "Mom or Dad isn't functioning correctly" to the awful word "Alzheimer's." That can be quite long, like five or ten years.

People with the disease have typically not wanted to know. They have wanted to deny it. It's hard to take the steps to arrive at -- and accept -- the diagnosis. A lot of general practitioners let sleeping dogs lie, because if we label it as Alzheimer's, what can the afflicted do? There are no great treatments available. You can't really blame the doctors. If you can break through the denial of the patient, a lot of current treatments, like Aricept, have very mixed results.

But this is all going to change. It's critical to break into the cycle of awareness, and that will require a lot of education. It will be important for people to have a good first treatment, so they will be willing to continue with treatments.

If you suspect or you have confirmation of a diagnosis, get into a therapeutic trial. Try to get medication. If there's a trial near you, get involved. Assert your rights for yourself.

What should caregivers know about Alzheimer's that isn't widely reported already?

CW: The saturation of amyloid is just wrong. What we're working on is absolutely not new. So there's a lot of misinformation out there. We are working to correct misperceptions so that, after our trial is successful, we'll be able to implement a tau-based treatment that will make a difference in people's lives expeditiously. We need to move on from mistakes and wasted time. Society matters more than people's reputation and careers.

Finally, what do you think the caregiving response to Alzheimer's will look like a few years down the road?

CW: It is going to be a completely different world. It used to be that hypertension and high lipids were in the domain of the cardiologist. That's how we have to imagine Alzheimer's disease. The tools and treatments will be there at the more widespread general-practitioner level to intervene early. I know the stress and pain that's out there -- it's not theoretical to me. It's really grim out there. There's huge suffering, often quiet and unspoken and no real awareness. Just consumed and swallowed. People hang in there out of a sense of duty and love for far too long. But it's counterproductive. Increasingly, the focus needs to be on true workable treatments so that we relieve the burden off of caregivers who are tasked with the impossible task of making decisions about a loved one's decline.

We have to help that -- we develop the tools but we have to be advocates to make sure they are in widespread use. Radical change could happen in the next few years. It's not that far away. We are really in the last lap -- not a long way off. Our treatment could be on the market by 2016.

You wear two hats, as scientist and head of a company that might produce a groundbreaking treatment. How do you reconcile the two?

CW: I do have a responsibility to shareholders, but my focus is on creating the treatment that will work. While it does worry me that the prices for medication will be high, I think that, in the end, the market works it out for you. There's a trade-off between market and volume of sales.

How ironic. Given how widespread Alzheimer's is now, with huge increases expected, the volume could work in favor to make treatments more affordable. Thanks for speaking with me today. Do you have a final thought about Alzheimer's and the future?

CW: My big dream is that this whole space will be transformed and people like me will be redundant except for hard cases, difficult social problems, and new developments. We face it, we name it, and we get on with taking care of it.

Dave Singleton

Dave Singleton is an award-winning writer, editor and author, who writes for numerous publications and websites on a variety of topics, including health, caregiving, pop culture, food, travel, social trends, relationships, and LGBT life. See full bio