Loss of Serotonin – a Happy Hormone – May Play a Role in Alzheimer’s

Serotonin is a neurotransmitter that also acts as a hormone. Many people know it as a mood booster, and low levels are linked with depression. A new study has also linked its loss with Alzheimer’s, which may provide doctors with a target for the disease’s progression.

Research recently published in the Journal of Alzheimer’s Disease investigated serotonin transporter levels and amyloid-beta build-up in the brains of patients with mild cognitive impairment, which can be a precursor to Alzheimer’s. They found that, compared with healthy peers, MCI patients had lower levels of serotonin transporter in several different areas of the brain.

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Dr. Gwenn Smith, the study’s first author and professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, says, “The study shows that people with mild cognitive impairment already display loss of the serotonin transporter. This measure that reflects serotonin degeneration is associated with problems with memory, even when we take into account in our statistical model MRI measures of neurodegeneration and PET measures of the amyloid protein that are associated with Alzheimer’s Disease.”

The study involved 49 volunteers 55 and older with mild cognitive impairment, a condition that involves an early form of memory loss and cognitive issues, and 45 cognitively healthy peers. The participants were each given MRIs and positron emission tomography scans of their brains at Johns Hopkins between 2009 and 2022. The researchers then studied the brains’ levels of serotonin transporter and amyloid-beta protein – a hallmark of Alzheimer’s.

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They found that patients with MCI had up to 25% lower serotonin transporter levels in cortical and limbic regions than the control group. There were also lower levels in the subcortical region. These regions are responsible for executive function, emotion, and memory. The findings back up other Johns Hopkins research that found in mice, a loss of serotonin is observed before amyloid-beta builds up in the brain.

Because lower serotonin is also linked with common conditions like depression and anxiety, there are existing medications that could potentially benefit MCI or Alzheimer’s patients, if more research backs up the findings.

Dr. Smith says, “The correlation we observed between lower serotonin transporters and memory problems in MCI is important because we may have identified a brain chemical that we can safely target that may improve cognitive deficits and, potentially, depressive symptoms. If we can show that serotonin loss over time is directly involved in the transition from MCI to AD, recently developed antidepressant medications may be an effective way to improve memory deficits and depressive symptoms and thus, may be a powerful way forward to slow disease progression.”

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The team is currently studying how these medications could help. They say future studies should also include longer follow-up with MCI patients to see how serotonin loss compares with an increase in amyloid-beta levels.

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