Orexin: It Will Wake You Up And You Won't Remember Why

    The body has a natural circadian rhythm that occurs on a 24-hour cycle, causing us to become sleepy at night and feeling awake (well sometimes) during the day. The cycle can still be scene even without any light cues present. The onset of Alzheimer's disease was linked to a molecule that regulates your sleep cycle. This molecule is orexin.

Orexin is a key player in this capability; it is responsible for the wakefulness that gets us up every morning. Orexin is naturally produced by a few number of cells (10,000-20,000) within the hypothalamus that are connected to the bodies circadian rhythm sequence (Paddock). 

Researchers from the School of Medicine at Washington University in St. Luis linked the connection that lower levels of orexin correlated with lower levels of brain plaques. Brain plaques are clumps of amyloid beta protein fragments that build up between nerve cells in the brain, disrupting their connections. These brain plaques are the hallmark sign of Alzheimer's disease (Paddock). Intuitively, with lower levels of orexin also means increased amounts of sleep and a well-known function of sleep is to heal or repair any damages the body may need to fix. So, is it the fact that the body is sleeping that reduces the risk of Alzheimer's disease or is it orexin itself that is responsible for the decrease in the amount of brain plaques?

As it turns out, it is the prior. Getting a sufficient amount of can be a preventative to Alzheimer’s disease. Sleep loss contributes to an increased level of plaques on the brains neurons, eventually leading to an increased risk of dementia. Orexin is a key target and to be able to block orexin and increase the length and quality of sleep can promote brain health.

A study with mice lacking orexin slept longer and deeper, while developing only one half as many brain plaques. However, there was a downside; when orexin deficiency was located in a specific area of the brain that is commonly effected by Alzheimer’s, the mice slept the same amount of time and the level of brain plaques did not reduce (Paddock).

So here is what we have so far. Orexin: a molecule known to control wakefulness that is associated with Alzheimer’s prevention when levels are reduced because brain plaques are also reduced. As it turns out a decrease in orexin does not directly control the amount of brain plaques, but allows for more sleep to occur, and sleep is the actual preventative aspect. Localized reduction of orexin does not work and must be reduced throughout the whole brain to have an effect.

Why do we care? Well, this is a big step in connecting the dots and understanding how this terrible disease works. This could contribute to preventative treatments like giving those who are at high risk for Alzheimer’s sleeping pills. Or develop a drug that can mimic sleeps healing effect and reduce brain plaques.

Although this may not be the answer, it is a puzzle piece to the cure.

Paddock, Catharine. "Targeting Sleep-wake Protein May Prevent Alzheimer's." Medical News Today. MediLexicon International, 26 Nov. 2014. Web. 30 Nov. 2014. <http://www.medicalnewstoday.com/articles/286192.php>.