• Posted December 11, 2023

Brain Serotonin Levels May Play Role in Alzheimer's Onset

Loss of the “happiness” brain hormone serotonin might play a role in the decline of brain function as a person ages, a new study reports.

People with mild cognitive impairment (MCI) had up to 25% lower levels of serotonin than healthy people in key regions of the brain associated with memory, problem-solving and emotion, researchers reported recently in the Journal of Alzheimer's Disease.

Those patients also had higher levels of amyloid beta, a protein that forms toxic clumps in the brains of Alzheimer's patients, the researchers added.

“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,” said researcher Gwenn Smith, a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine in Baltimore.

“If we can show that serotonin loss over time is directly involved in the transition from MCI to AD [Alzheimer's disease], 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,” Smith added in a Hopkins news release.

For this study, researchers recruited 49 volunteers with mild cognitive impairment and 45 healthy adults aged 55 and older to undergo brain scans. The scans measured changes in brain structure between 2009 and 2022.

Mild cognitive impairment is the middle ground between normal brain function as people age and Alzheimer's disease. Symptoms include frequent forgetfulness of recent events, difficulty finding the right word, and loss of the sense of smell.

People who develop MCI might remain in that state indefinitely, or progress to dementia and Alzheimer's, researchers said.

They looked specifically at serotonin, a brain chemical long associated with positive mood, appetite and sleep. Loss of serotonin is often associated with depression, anxiety and psychological disorders.

Mouse studies previously conducted at Johns Hopkins have shown that serotonin loss occurs before the development of widespread amyloid beta plaques in the brain, researchers said.

“The [latest] study shows that people with mild cognitive impairment already display loss of the serotonin transporter,” Smith said. “This measure that reflects serotonin degeneration is associated with problems with memory, even when we take into account” amyloid plaques and other signs of brain degeneration associated with Alzheimer's.

Future studies are needed to more precisely track the loss of serotonin and the increase in amyloid beta in the brains of people with MCI, researchers said.

Researchers also would like to track levels of tau, another protein associated with Alzheimer's disease.

This study's design couldn't show why serotonin loss might prompt loss of brain function, or prove a direct cause-and-effect relationship between serotonin and thinking declines.

More information

Harvard Medical School has more about Alzheimer's disease.

SOURCE: Johns Hopkins School of Medicine, news release, Dec. 7, 2023