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Effects of Alzheimer's disease reversed in mice

Press Trust of India  |  Washington 

In a first, scientists have reversed the effects of in mice, paving the way for treatments to cure the neurodegenerative in humans.

Reversing and impairments in spatial learning is a major goal in the field of research. A lack of knowledge about cellular pathways critical to the development of dementia, however, has stood in the way of significant clinical advance.

Researchers at in the US are breaking through that barrier. They show, for the first time in an animal model, that tau pathology - the second-most important lesion in the brain in patients with - can be reversed by a drug.

"We show that we can intervene after disease is established and pharmacologically rescue mice that have tau-induced memory deficits," said Domenico Pratico, a at

The study, published in the journal Molecular Neurobiology, raises new hope for human patients affected by

The researchers landed on their breakthrough after discovering that known as leukotrienes are deregulated in and

In experiments in animals, they found that the leukotriene pathway plays an especially important role in the later stages of disease.

"At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage," Pratico said.

"Having discovered this, we wanted to know whether blocking leukotrienes could reverse the damage, whether we could do something to fix memory and learning impairments in mice having already abundant tau pathology," he said.

To recapitulate the clinical situation of in humans, in which patients are already symptomatic by the time they are diagnosed, researchers used specially engineered tau transgenic mice, 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, a drug that inhibits leukotriene formation by blocking the 5-lipoxygenase enzyme.

After 16 weeks of treatment, animals were administered maze tests to assess their working memory and their spatial learning memory.

Compared with untreated animals, tau mice that had received zileuton performed significantly better on the tests. Their superior performance suggested a successful reversal of

To determine why this happened, the researchers first analysed leukotriene levels. They found that treated tau mice experienced a 90 per cent reduction in leukotrienes compared with untreated mice.

In addition, levels of phosphorylated and insoluble tau, the form of the protein that is known to directly damage synapses, were 50 per cent lower in treated animals.

Microscopic examination revealed vast differences in synaptic integrity between the groups of mice. Whereas untreated animals had severe synaptic deterioration, the synapses of treated tau animals were indistinguishable from those of ordinary mice without the disease.

"was completely gone from tau mice treated with the drug. The therapy shut down in the brain, allowing the tau damage to be reversed," said Pratico.

The study is especially exciting because zileuton is already approved by the for the treatment of

"Leukotrienes are in the lungs and the brain, but we now know that in addition to their functional role in asthma, they also have a functional role in dementia," 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 said.

(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)

First Published: Sun, June 10 2018. 11:15 IST
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