Where Does Tau Fit In?

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“Amyloid” is a generic term for numerous different fibrous protein structures that are present naturally in the human body. While some of them have a normal function, many have been associated with disease and neurodegenerative disorders. Beta amyloid (Aβ) and tau amyloid are the two types specifically associated with Alzheimer’s disease (AD).

Normal tau has a microtubule shape and is designed to help transport food and other molecules into nerve cells. In AD, tau becomes misshapen into toxic neurofibrillary tangles.

In advanced Alzheimer’s, the brain becomes littered with tau tangles and Aβ plaques. Which came first was a “chicken and egg” question, and for a long time, researchers debated the respective influence of amyloid vs. tau on developing AD.

Reisa Sperling, MD portrait
Reisa Sperling, MD

A consensus has emerged that it’s not one or the other; it’s both. "The combination of amyloid and tau is really the toxic duo," said Reisa Sperling, MD, of Harvard, in a New York Times interview. It’s hypothesized that AD starts with Aβ accumulation, and that abnormal Aβ levels bring other changes, including the spread of toxic tau. At that point, damage to the brain seems to accelerate.

Sperling is a 2010-13 BrightFocus grantee who helped pioneer Aβ imaging with PET scans. Now a co-leader of the A4 study, she and colleagues recently announced that tau imaging will be done on a subset of 500 participants. With thrice-yearly scans collected over a three-year period, much more will be known about tau in the future. Another hypothesis being pursued is that Aβ and tau accumulation in the Alzheimer’s brain is not due to increased production, but impaired clearance. In other words, something causes cells to stop taking out the trash. This idea, just reported in Brain by Krohn et al, also is being explored in several active BrightFocus grants. Researchers are looking for genetic signaling and other disruptions that might interfere with Aβ clearance, and how to stop that from happening. —Martha Taggart, BrightFocus Health and Science Writer