A fascinating new study from researchers at Temple University has successfully reversed cognitive impairments in mice with dementia. The research utilized a 20-year-old asthma drug to treat the animals and the hope is to fast track clinical trials to verify the results in human subjects.

The general hypothesis in most current Alzheimer's research is that the cognitive degeneration associated with the disease is primarily caused through a build-up of amyloid beta proteins in the brain. This results in a clumping of protein fragments called plaques, and a great deal of modern study is focusing on that particular pathway to try and come up with a clinical treatment.

This "amyloid hypothesis" is not 100 percent agreed on, though, and a variety of researchers are starting to look in other places for a better way to effectively treat Alzheimer's disease and its dementia-related conditions. A growing body of evidence is beginning to suggest that examining another protein target called tau could lead to more effective future treatments.

Tau is a protein that has been strongly implicated in the pathology of Alzheimer's and dementia, with some researchers going so far as to hypothesize it, and not amyloid, is the primary causative agent behind the degenerative disease. The idea is that these tau proteins can begin to form abnormal clumps called neurofibrillary tangles, which accumulate inside neurons and ultimately may be the driving force behind the neurodegeneration that goes along with Alzheimer's.

The new Temple University research set out to better understand the pathology behind this abnormal tau accumulation and began by homing in on an inflammatory molecule known as a leukotriene. In later-stage Alzheimer's and dementia it had been observed that leukotrienes are over expressed and deregulated, suggesting these inflammatory molecules play a significant part in the onset of dementia.

"At the onset of dementia, leukotrienes attempt to protect nerve cells, but over the long term, they cause damage," says Domenico Praticò, a senior investigator on the new research. "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."

The research looked to a drug called zileuton, known to inhibit leukotriene formation, and safely administered to patients with asthma for over 20 years. The experiments treated specially engineered mice with the drug. The mice were developed to specifically replicate a degenerative tau pathology so when they are 12 months old, they show the same brain degeneration as a 60-year-old human with early-onset dementia symptoms.

The results were undoubtedly impressive. After 16 weeks, the mice treated with zileuton performed significantly better on several memory tests compared to the untreated animals. The treated mice also displayed 90 percent fewer leukotrienes than their counterparts and 50 percent less insoluble tau, the protein form thought to damage synapses.

"Inflammation was completely gone from tau mice treated with the drug," says Praticò. "The therapy shut down inflammatory processes in the brain, allowing the tau damage to be reversed."

It is this explicit reversal of brain damage that is the most remarkable aspect of the study. Examining the synapses of the animals, the researchers noted that the treated animals displayed no evidence of synaptic deterioration, while the untreated animals showed severe synaptic damage. This suggests that the zileuton treatment actively reversed any tau-related brain damage in the animals.

This research is still obviously in an early stage and it is important to note that there is no guarantee the results will translate across to human subjects. However, the fact that the study utilized a drug that is already cleared and approved for human use means it should be a speedy path to human clinical trials. And, even if this particular drug does not prove fruitful in human subjects, it may stimulate other researchers to spend more time looking into tau and other hypotheses to help develop new treatments for Alzheimer's and dementia.

The study was published in the journal Molecular Biology.