Nature Medicine | Spoonful of Medicine

The Tau of combating Alzheimer’s

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The main culprit behind Alzheimer’s disease has long thought to be the toxic protein beta-amyloid, which forms diffuse plaques in the brain. As such, most researchers have assumed that the nerve cell-engulfing tangles caused by a second protein called tau were mere consequences of the amyloid plaques. But given the failure of current amyloid-targeting drugs to reverse the course of the devastating neurodegenerative disorder, the plaque theory has been waning.

In its place, the focus is shifting over to blocking tau. In a series of new studies reported yesterday at the International Conference on Alzheimer’s Disease in Honolulu, Hawaii, researchers reported four new experimental therapies that either target tau directly or mediate levels of both tau and beta-amyloid conjointly.

In one study, a team led by Kaj Blennow of the University of Gothenburg in Sweden looked at the effects of an experimental drug called bapineuzumab, which had been designed to reduce clumps of amyloid-beta. Blennow’s team analyzed spinal fluid samples from two phase 2 clinical trials, and found that patients given bapineuzumab — which is being developed jointly by Pfizer, Elan Corp and Johnson & Johnson — had significantly lower levels of tau in their brain. These findings add to a small imaging study, published in April in Lancet Neurology, showing that drug cut amyloid levels in the brain by 25%.

Independently, Delphine Boche of the University of Southampton, UK and her colleagues investigated levels of tau in patients given a beta-amyloid immunotherapy as part of a phase 2 trial that had to be stopped early after a few participants developed serious brain inflammation. The researchers found that immunized Alzheimer’s subjects had significantly less tau in their dendrites compared to unimmunized controls.

“The findings show that treatment aimed at beta amyloid may also modify tau changes in Alzheimer’s,” Boche said in a press release.

Two research teams also reported findings from new rodent models of Alzheimer’s. Allal Boutajangout of the New York University School of Medicine treated diseased mice with a monoclonal antibody called PHF-1 and found that mice performed better than controls in a balance test and had 58% less tau pathology in the brain’s hippocampus. Meanwhile, Michal Novak of the Slovak Academy of Sciences in Bratislava developed a new transgenic rat model of Alzheimer’s rat that expresses non-mutated tau yet can generate Alzheimer’s tangles. Immunizing the rats with a mutated version of tau, Novak announced, prevented the tangle development and slowed the loss of learning behaviors.

“It is very important that we have a variety of therapeutic targets in the fight against Alzheimer’s disease,” William Thies, chief medical and scientific officer at the Alzheimer’s Association, said in a press release. “The more opportunities that we investigate to intervene and change the relentless and progressive course of Alzheimer’s, the better chance that we will find something that works.”

Image of tau tangles via Wikimedia Commons

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