U.S. scientists claim reducing levels of the protein tau prevents the characteristic blockages in axonal transport caused by amyloid beta (Aβ) proteins in the brains of patients with Alzheimer disease. The Gladstone Institute of Neurological Disease (GNID) team hopes that blocking tau may represent a new strategy to Alzheimer therapy that works by making the brain more resistant to the detrimental effects of Aβ build-up.
The research, by GNID director Lennart Mucke, M.D., and colleagues, built on their previous studies which suggested that blocking tau expression prevents Aβ from causing memory deficits and other abnormalities in mouse models of Alzheimer disease. “We wondered whether this striking rescue might be caused, at least in part, by improvements in axonal transport,” comments Dr. Mucke, who is also the Joseph B. Martin distinguished professor of neuroscience at UCSF.
To explore this hypothesis further, the GNID researchers cultured neurons from normal mice and from animals lacking one or both tau genes. When they exposed these neurons to human Aβ proteins, axonal transport slowed significantly in the neurons that still expressed tau. Conversely, the tau knockout neurons continued to demonstrate normal axonal transport.
“We are really excited about these results,” adds GNID’s Keith Vossel, M.D. “Whether tau affects axonal transport or not has been a controversial issue, and nobody knew how to prevent Aβ from impairing this important function of neurons. Our study shows that tau reduction accomplishes this feat very effectively.”
The researchers admit that much research will be needed before the approach can be extrapolated to humans, but claim tau reduction does “look promising in this regard,” Dr. Mucke concludes.
The GNID team’s findings come within days of Roche and reMynd announcing a potentially $636,000 deal to develop the latter’s preclinical pipeline that includes candidates targeting tau-related toxicity in Alzheimer disease.