Tau protein is the second-most important lesion in the brain causing memory deficits and impairments in spatial learning among patients with Alzheimer's, the first being abnormal levels of beta-amyloid proteins that clump together to form plaques that collect between neurons and disrupt cell function.
In the study, researchers from Temple University in Pennsylvania, US, engineered mice with abnormal levels of tau, which develop tau pathology -- characterised by neurofibrillary tangles, disrupted synapses (the junctions between neurons that allow them to communicate with one another), and declines in memory and learning ability -- as they age.
When the animals were 12 months old, the equivalent of age 60 in humans, they were treated with "zileuton" -- approved by the US Food and Drug Administration for the treatment of asthma.
The results, published in the journal Molecular Neurobiology, showed that mice treated with "zileuton" experienced a 90 per cent reduction in the formation of leukotrienes -- inflammatory molecules that are deregulated in Alzheimer's and related dementias.
In addition, levels of phosphorylated and insoluble tau, the form of protein that is known to directly damage synapses, were 50 per cent lower.
While untreated animals had severe synaptic deterioration, the synapses of treated tau animals were indistinguishable from those of ordinary mice without the disease.
"We show that we can intervene after the disease is established and pharmacologically rescue mice that have tau-induced memory deficits," said Domenico Pratico, Professor at the varsity.
After 16 weeks, the zileuton treated tau mice performed significantly better on maze tests, suggesting a successful reversal of memory deficiency.
"Inflammation was completely gone from tau mice treated with the drug. The therapy shut down inflammatory processes in the brain, allowing the tau damage to be reversed," Pratico said.
"This is an old drug for a new disease. The research could soon be translated to the clinic, to human patients with Alzheimer's disease," he noted.
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