How to prevent Alzheimer’s-associated traffic jams in the brain

WASHINGTON - Reducing the level a protein, tau, can prevent the traffic jams due to Alzheimer’s disease (AD) causing amyloid beta (AB) proteins, according to scientists at the Gladstone Institute of Neurological Disease (GIND).

AB proteins, which build up to toxic levels in the brains of people with AD, impair the axonal transport of these cargoes like mitochondria.

“We previously showed that suppressing the protein tau can prevent AB from causing memory deficits and other abnormalities in mouse models of AD. We wondered whether this striking rescue might be caused, at least in part, by improvements in axonal transport,” explained Dr. Lennart Mucke, director and senior author of the study.

The scientists explored this possibility in mouse neurons grown in culture dishes.

Neurons from normal mice or from mice lacking one or both tau genes were exposed to human AB proteins.

The AB slowed down axonal transport of mitochondria and growth factor receptors, but only in neurons that produced tau and not in neurons that lacked tau.

In the absence of the AB challenge, tau reduction had no effect on axonal transport.

“We are really excited about these results. Whether tau affects axonal transport or not has been a controversial issue, and nobody knew how to prevent AB from impairing this important function of neurons. Our study shows that tau reduction accomplishes this feat very effectively,” said Dr. Keith Vossel, lead author of the study.

“Some treatments based on attacking AB have recently failed in clinical trials, and so, it is important to develop new strategies that could make the brain more resistant to AB and other AD-causing factors. Tau reduction looks promising in this regard, although a lot more work needs to be done before such approaches can be explored in humans,” said Mucke. (ANI)