Tangled Up in Tau

Massachusetts General
  • Anita Slomski

Neurologist Bruce Miller calls tau—a floppy, free-form protein—“the holy grail of dementia.” That designation may come as a surprise to anyone who has even a passing interest in the science of end-of-life brain diseases. A different protein, amyloid-beta (Aß), has become famous as the culprit responsible for the so-called senile plaques that gum up the brains of people with Alzheimer’s disease. Yet tau also plays a role in Alzheimer’s, by far the most prevalent type of dementia, and it’s not Aß but tau, escaping its proper place inside neurons, that attacks the brain in a host of similar diseases.

According to Miller, who heads the Memory and Aging Center at the University of California, San Francisco, and the Tau Consortium, an international research program, knowledge of Aß emerged before much was known about tau. As a result, pharmaceutical companies have invested considerable sums developing therapies that target Aß. Yet so far, all trials attempting to clear Aß plaques from the brain have failed to slow down the disease or to produce any cognitive improvement in people with early stages of Alzheimer’s disease.

As discoveries about tau were made, however, it became increasingly clear that the protein may be a major contributor to many kinds of dementia, which could be more closely related to one another than anyone had guessed. “We’ve gone from thinking of tau as not very interesting to understanding that tau pathology leads to multiple diseases that have different clinical symptoms based on which brain region and type of neurons are affected,” says Michel Goedert, head of the neurobiology division at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. In 1996, he and Bernardino Ghetti of Indiana University coined the term tauopathy to describe diseases that have tau inclusions as their common, defining denominator.

Among the more than two dozen tauopathies is frontotemporal dementia (FTD), which leads to impaired social skills, language loss and personality changes. Another, corticobasal degeneration, causes the rigidity and abnormal postures of Parkinson’s disease as well as difficulty with speech and swallowing and the perception that an arm or a leg isn’t part of your own body. There’s also progressive supranuclear palsy, characterized by balance and eye problems, depression, apathy and dementia. Still another tauopathy—chronic traumatic encephalopathy—may arise in football players, war veterans and others who have suffered repeated concussions or other brain trauma.

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