Low Serotonin Levels May Be Linked to Development of Alzheimer's

As the future becomes the present then the past, scientists, doctors, and patients alike learn more and more about Alzheimer’s disease and how it develops.

Today, researchers are learning about the role serotonin plays in the progression of this disease. While the causes of Alzheimer’s are not yet known, one potential suspect is serotonin, an important neurotransmitter.

It is known that people with Alzheimer’s have lower levels of serotonin than their healthy counterparts. What is not yet fully known is whether the Alzheimer’s causes the low serotonin, or if a lack of serotonin causes Alzheimer’s.

Some researchers from the John Hopkins University School of Medicine in Baltimore, Maryland, looked at this conundrum and tried to figure out the relationship.

Well-Being and Happiness

Serotonin is a monoamine neurotransmitter, also called 5-hydroxytryptamine or 5-HT. Broken down, this means it is made from a single amino acid (in this case, tryptophan) and is one of the chemical messengers the brain uses to communicate with itself and the body. A neurotransmitter carries a message from a nerve cell to another cell, be it a nerve cell, muscle cell, or gland cell.

This particular neurotransmitter has many effects on the body. Generally, it helps to regulate things such as mood and sexual function. It also affects sleep and diet, so it has an effect on your overall wellbeing. In fact, while serotonin is very active in the brain, most of the serotonin in your body is active in your gastrointestinal tract.

Serotonin also affects cognitive functions such as memory and learning. When levels of serotonin are deficient, then the result can be anxiety, problems sleeping, weight gain, sugar cravings, and depression.

Once a serotonin receptor has been activated by serotonin then it releases other neurotransmitters. There are many of those, such as dopamine, epinephrine and norepinephrine, glutamate, and GABA. Hormones are also released, such as cortisol, oxytocin, prolactin, and vasopressin.

There are many types of serotonin receptors, also called 5-HT receptors.

Serotonin does not move itself around. It is carried by a protein called serotonin transporter, also known as SERT. After transporting serotonin, it terminates the action of the neurotransmitter then brings it back for recycling.

Most antidepressant medications, such as SSRIs, target serotonin transporter instead of serotonin itself. They prevent the transporter from reuptaking and recycling serotonin, thus keeping more of the neurotransmitter active between the nerve cells.

People with Alzheimer’s have lower levels of serotonin than other people. Not only that, but they also tend to have less of the neurons which modulate serotonin. That loss is associated with excessive amounts of beta amyloid, a protein, which results in the formation of plaque deposits in the brain.

Those plaque deposits are one of the strongest indicators of Alzheimer’s disease, and can be seen even before cognitive symptoms develop.

Gwenn Smith, PhD and professor of psychiatry and behavioral sciences at the John Hopkins University School of Medicine, wanted to investigate this link to identify if the relationship between serotonin and Alzheimer’s was causal or not. Let’s examine her findings.

Studying Serotonin

For this study, Gwenn Smith was joined by Frederick Barrett, Jin Hui Joo, Najlla Nassery, Alena Savonenko, Devin Sodums, Christopher Marano, Cynthia Munro, Jason Brandt, Michael Kraut, Yun Zhou, Dean Wong, and Clifford Workman. Their study, titled Molecular imaging of serotonin degeneration in mild cognitive impairment was published in the Neurobiology of Disease journal on September 2017.

There were 56 participants in the study. On average, they were 66 years of age, and just under half were female. Positron emission tomography scans, aka PET scans, were used to examine the levels of serotonin in order to determine the behavior of SERT in the participants’ brains.

A radioactive carbon isotope was used which highlighted SERT in the scans.

Half of the participants had symptoms of mild cognitive impairment, which is a known precursor to Alzheimer’s disease. This was determined through the use of standard cognitive assessments. The other half was the control group and was formed of healthy adults.

They also used these scans to determine the amount of beta amyloid build-up in the brains of the participants to gauge the potential future cognitive decline of the volunteers.

Results

Every single participant with mild cognitive impairment had lower levels of SERT than any of the healthy members of the control group. In some cases, this was as much as thirty eight percent lower. Even when matched to people of the same age; the reduction of serotonin transporter was greater than the amount of gray matter atrophy seen by similarly aged counterparts.

Cerebral blood flow as also observed, and like the case of grey matter atrophy, was not linked to cognitive decline nearly as much as a reduction in serotonin transporter levels.

In addition, the decreased amount of SERT strongly correlated with the standardized cognitive tests. The lower their recorded level of serotonin transporter, the more poorly they performed on the tests. This reduction in the amount of serotonin transporter was not a mild correlation, the results were robustly statistically significant.

An eighteen percent reduction in the amount of serotonin transporter correlated with a thirty seven percent worse score in the verbal memory test, when comparing people with mild cognitive decline against their healthy counterparts of the same age.

According to Gwenn Smith, PhD, “now that we have more evidence that serotonin is a chemical that appears [to be] affected early in cognitive decline, we suspect that increasing serotonin function in the brain could prevent memory loss from getting worse and slow disease progression.”

The researchers believe that fighting the loss of serotonin may be beneficial to slow down the progression of Alzheimer’s, or even completely stop the degeneration.

Transporters or Receptors

As mentioned before, the general way to combat low levels of serotonin is to inhibit their reuptake, preventing them from being reabsorbed and recycled, so they affect the other nerve, muscle, or gland cells for longer.

One of the attempted treatments for Alzheimer’s has been through the use of SSRIs, which try to increase the amount of serotonin available. Unfortunately, for people in the process of developing Alzheimer’s, this has not been shown to be successful.

That reason may be because SSRIs bind to serotonin transporters in order to prevent their reuptake, and those are precisely what is missing in people with Alzheimer’s disease. Gwenn Smith, PhD, therefore recommends to scientists trying to apply this knowledge towards a treatment to target the serotonin receptors rather than the transporters.

It may be possible to substitute serotonin with another neurotransmitter which may help the body produce the same effects.

Increasing the amount of serotonin produced, such as by consuming the building blocks for the neurotransmitter including but not limited tryptophan and omega 3 fatty acids, may help. Other activities, such as exposure to natural light, also increases the amount of serotonin produced.

However, this may not be as helpful as it could be, since the serotonin transporter levels will also be low. But giving them more to transport may result in more serotonin transported total. As Alzheimer’s is a progressive disease, even a little bit of slowing it down in the beginning can help in the long run.

Final thoughts

It has long been known that people with Alzheimer’s have a lower level of serotonin than people of the same age without such cognitive degeneration. Serotonin levels may not be a product of Alzheimer’s, however, and may contribute to its development.

Increasing serotonin function in the brain may help lead to a reduction in the development of Alzheimer’s disease. The best way to counter low serotonin levels in such affected people has not yet been discovered. SSRIs are ineffective, as the reason for the low amount of serotonin is because of the lack of serotonin transport proteins.

But the way is laid open for someone to develop the treatment by which serotonin levels in Alzheimer’s patients may be raised to a healthy level.

References

http://www.medicalnewstoday.com/articles/318968.php

http://www.sciencedirect.com/science/article/pii/S0969996117301109