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Caffeine boosts enzyme that could protect against dementia

By Connie Wan, P.h.D | December 4th, 2017

Caffeine has well-known short-term stimulating effects on central nervous system, but the long-term impacts on cognition have been less clear. Scientists from Indiana University (IU) just gave those of us, who live on coffee and tea, another reason to enjoy that steaming cup of mocha. It turns out that caffeine not long gives you that extra boost in the morning but also protects you against dementia in the old age.

A study by Indiana University researchers has identified caffeine, one of the 24 compounds with the potential to boost an enzyme in the brain shown to protect against dementia.1 The protective enzyme, called NMNAT2, plays two roles in the brain: a protective function to guard neurons from stress and a “chaperone function” to combat misfolded proteins, which accumulate in the brain as “plaques” due to aging. Misfolded proteins have been linked to neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases, as well as amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease.

To identify substances with the potential to affect the production of the NMNAT2 enzyme in the brain, the researchers screened over 1,280 compounds, including existing drugs. A total of 24 compounds were identified as having potential to increase the production of NMNAT2 in the brain. One of the substances shown to increase production of the enzyme was caffeine, which also has been shown to improve memory function in animal model genetically modified to produce high levels of misfolded proteins. To confirm the effect of caffeine, IU researchers administered caffeine to mice modified to produce lower levels of NMNAT2. As a result, the mice began to produce the same levels of the enzyme as normal mice. This means that caffeine increased the production of the protective enzyme in the brain and therefore could potentially lead to the protection of the brain against the dementia.

This UI research supports earlier epidemiology studies showing the protective effect of caffeine in dementia and Alzheimer’s disease. For Example, the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study by Finland researchers in 2010 showed that coffee drinking of 3-5 cups per day at midlife was associated with a decreased risk of dementia/AD by about 65% at late-life.2 The Finland researchers hypothesized that the correlation may be mediated by caffeine and/or other mechanisms like antioxidant capacity and increased insulin sensitivity. The UI research seems to confirm that caffeine is a key factor for the brain protecting effect of the coffee.

Thanks for reading.

Journal Reference:

  1. Yousuf O. Ali, Gillian Bradley, Hui-Chen Lu. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons. Scientific Reports, 2017; 7: 43846 DOI: 10.1038/srep43846
  2. Eskelinen MH1, Kivipelto M. Caffeine as a protective factor in dementia and Alzheimer’s disease, J Alzheimers Dis. 2010; 20 Suppl 1:S167-74. doi: 10.3233/JAD-2010-1404.

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