Mayo Clinic team renews Alzheimer's feud, fingers tau over amyloid

In the world of Alzheimer's drug research, there's no lack of certainty among leading researchers. There's just no consensus on what causes the disease or how to treat it. 

The amyloid beta theory has a whole contingent of zealous advocates who say there can be no doubt that the toxic protein triggers the disease. But tau has its own set of die-hard backers, and now there's a new study from the Mayo Clinic to back their pitch.

Melissa Murray

Studying hundreds of brains at various stages of developing Alzheimer's, a team led by Melissa Murray at the Mayo Clinic in Jacksonville, FL, says that they were able to conclusively determine that the accumulation of abnormal tau in neurons lays waste to them, triggering a process in which the toxic tau spreads throughout the cortex, killing cells in a region of the brain that plays a major role in higher level thinking.

"Amyloid, on the other hand, starts accumulating in the outer parts of the cortex and then spreads down to the hippocampus and eventually to other areas," says Murray. "Our study shows that the accumulation of amyloid has a strong relationship with a decline in cognition. When you account for the severity of tau pathology, however, the relationship between amyloid and cognition disappears--which indicates tau is the driver of Alzheimer's." 

Murray's certainty, though, will do nothing to end the debate at this point of the game. A wide range of Big Pharmas--including Johnson & Johnson ($JNJ), Pfizer ($PFE), Eli Lilly ($LLY) and others--has poured billions of dollars into developing drugs that can either flush amyloid or prevent its development. So far, they've all failed in the clinic, but with millions of patients facing a disease that they can neither stop nor slow, there's still plenty of clinical work going on. Biogen ($BIIB) recently touted their own early success in the field, laying out plans to go straight into Phase III with an amyloid drug.

Tau, on the other hand, has had fewer advocates. But they are no less passionate about their opinions. And there are a number of investigators that straddle the line. J&J, for example, recently partnered with AC Immune on tau, collaborating with a biotech that has close ties with Roche ($RHHBY) on a separate approach with amyloid. And company execs say it will likely take a combination approach to truly have an impact on the disease.

- here's the press release
- read the research article

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