Can the symptoms of Alzheimer’s be reversed? As of right now, it is not so for humans, but Senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer’s Center at Temple at Lewis Katz School of Medicine(LKSOM), has found a way to accomplish this for mice. His study which is published in the online journal Molecular Neurobiology raises new aspirations for dementia patients.
One of the most important goals in dementia research is to reverse memory loss symptoms. However, due to the lack of knowledge on cellular pathways important to the development of dementia, no further progress has been made. Now, researchers at LKSOM are making progress by reversing tau pathology in mice. Tau pathology are human neurodegenerative diseases caused from the pathway from soluble tau protein to insoluble tau protein in the human brain. It is characterized by damaged synapses ( junctions between neurons that allow them to communicate with one another).The dysfunction of tau proteins in our brains causes different disorders that cause dementia. That’s why Dr. Praticò's findings are significant, it deals with one of the core sources of dementia.
Dr. Praticò and his fellow researchers came across their findings when they discovered that leukotrienes (inflammatory molecules in the brain) play an important role in the later stages of dementia. Dr. Praticò said in his study, “At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage. 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 tay pathology”.
To test this, the researchers created a simulation where they specially engineered mice with tau protein, who will eventually develop tau pathology. When the mice became 12 months old (equivalent to 60 human years) they were treated with zileuton, a drug that blocks leukotriene formation. 16 weeks after the drug was given to some of the mice, the animals took maze tests to evaluate their memory. The tau mice that received the drug performed significantly better than the ones that didn’t, showing evidence for the reversal of memory loss. Researchers analyzed the mice to find out why the drug worked. According to Temple Health, “They found that treated mice experienced a 90-percent reduction in leukotriene levels compared with untreated mice. In addition, levels of insoluble tau protein (the form of protein that is known to directly damage synapses), were 50 percent lower in treated animals. Microscopic examination revealed the vast differences in synaptic integrity between the groups of mice. Whereas untreated animals had synaptic deterioration, the synapses of treated tau mice were indistinguishable from those of ordinary mice without the disease”. Dr. Praticò added that the therapy stopped the inflammation in the brain, allowing the damage to be fixed.
Zileuton is an approved drug as a treatment for asthma. Researchers knew that leukotrienes are already present in the brain and lungs, but now thanks to the latest study at LKSOM, we know that they play as big of a role in dementia as they do in asthma. Like Dr. Praticò said himself, “This is an old drug for a new disease”. The findings of Dr. Praticò and his fellow researchers could one day be translated into clinics and help patients suffering from dementia.
References: