Tauopathies are conditions in which accumulation of tau into neurofibrillary tangles causes dysfunction and cell death in the brain. Alzheimer’s disease is the best known of these neurodegenerative conditions. Researchers here demonstrate an approach to reducing both tau aggregation and inflammation in mice, based on inhibition of leukotrienes. Mouse models of neurodegenerative conditions based on protein aggregation are highly artificial, as these forms of aggregation do not naturally occur in that species. This can produce misleading results, or at least results that have to be carefully assessed in the full understanding of the biochemistry involved, and how it might differ from that of humans. That said, the approach here does use an established pharmaceutical compound, meaning that there is a comparatively short path towards validation of the mechanism in human patients.
Researchers have shown, for the first time in an animal model, that tau pathology – the second-most important lesion in the brain in patients with Alzheimer’s disease – can be reversed by a drug. The researchers landed on their breakthrough after discovering that inflammatory molecules known as leukotrienes are deregulated in Alzheimer’s disease and related dementias. In experiments in animals, they found that the