Dementia is a disease that mainly affects older people and is characterized by difficulties with coordination and speech, memory distortions, restlessness, and problems with perception. People with dementia also suffer from behavioural changes which can include depression, irritability, anxiety, apathy, and agitation. 20-40% of people over the age of 85 will be diagnosed with dementia and it will cause around 1.7 million deaths per year. Alzheimer’s disease is the most common cause of dementia, accounting for 60-70% of all cases. In Alzheimer’s, it is believed that a build up of abnormally folded proteins, called tau proteins, leads to the death of nerve cells and ultimately Alzheimer’s. New treatment options for Alzheimer’s and dementia have been focusing on preventing these tau proteins from forming or targeting them for destruction. A team of researchers last year identified an enzyme called NMNAT that was reduced in people with dementia and Alzheimer’s and seemed to play a role in preventing tau protein formation. Since this protein has shown some promise in being able to prevent neurodegenerative disorders like dementia, the same team of researchers set out to identify compounds that may be able to increase the levels of this enzyme as a possible treatment for dementia and Alzheimer’s.
The results, published in the journal Scientific Reports, screened a total of 1,280 compounds for the ability to increase the levels of NMNAT in neurons. Of the 1,280 compounds, 24 were identified that increased the levels of NMNAT and 13 were identified as decreasing the levels of NMNAT. One of the compounds shown to increase NMNAT levels was caffeine. This is interesting since previous research has shown caffeine consumption to be associated with a decreased risk of dementia and Alzheimer’s later in life. The results from this paper suggest a potential mechanism by which caffeine is protective. In fact, the researchers found that in mice made to be genetically susceptible to dementia, caffeine was able to return their levels of NMNAT to normal. In addition to caffeine, the researchers identified a drug that had previously been used in the treatment of depression but recently abandoned. This drug, Rolipram, was able to increase the levels of NMNAT just like caffeine and was able to prevent neuron death.
This paper provides good evidence that targeting the tau proteins by changing NMNAT levels could be a plausible way to treat dementia and Alzheimer’s. It also gives a mechanism to coffee’s anti-dementia effects. The next step is to determine if any of the identified compounds could be used in pre-clinical models to treat dementia. Caffeine is unlikely to be useful as the amount you would need to deliver would be huge, however Rolipram may find a new life as an anti-dementia or anti-Alzheimer’s drug.
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