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A brain showing decreases of
serotonin transporters (blue)
in the MCI group compared
to the healthy control group

Courtesy of Gwenn Smith lab

Researchers leverage PET and MR to uncover serotonin's role in Alzheimer's

by Lauren Dubinsky , Senior Reporter
Serotonin may have more to do with Alzheimer’s disease than previously thought.

A team at Johns Hopkins Medicine used PET and MR imaging to measure patients’ brain structures and levels of serotonin and found that lower levels may contribute to the onset of the disease. A report on this research was published in the September issue of Neurobiology of Disease.

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“The study shows that the serotonin system is affected in the early stages before memory problems are severe enough to meet criteria for dementia,” Dr. Gwenn Smith, professor and director of geriatric psychiatry and neuropsychiatry at the university, told HCB News. “We hope the study will stimulate development of medications targeting the serotonin system for use in individuals at risk for dementia.”

Previous studies have shown that Alzheimer’s and severe cognitive decline are associated with a significant loss of serotonin neurons, but it was unclear whether it was a cause or consequence of the disease.

Smith and her colleagues had 28 participants with mild cognitive impairment (MCI) and 28 healthy, matched controls undergo MR and PET exams. During the PET exams, a chemical labeled with a radioactive carbon was administered that’s similar in structure to an antidepressant, but not at a dose that would produce a pharmacological effect.

“Brain regions such as the hippocampus that are affected early in AD can be imaged in more detail with MR compared to CAT scans,” said Smith “Neurotransmitters in the brain such as serotonin and dopamine can only be imaged with selective radiotracers that are available for PET and SPECT imaging.”

They found that those with MCI had up to 38 percent less of the serotonin transporter SERT in their brains, compared to the health control group. None of the participants with MCI had higher levels of SERT than their healthy counterparts.

The participants also underwent learning and memory tests including the California Verbal Learning Test, which is scored on a scale of 0 to 80 with a higher number reflecting better memory. The healthy participants scored an average of 55.8 and those with MCI scored an average of 40.5.

For the Brief Visuospatial Memory Test, the participants were shown a series of shapes to remember and draw later. On a scale of 0 to 36, with 36 being the top score, the healthy group scored an average of 20 and those with MCI scored an average of 12.6.

The research team compared the results of the brain imaging tests with the two memory tests and found that lower serotonin transporters correlated with lower scores. For instance, those with MCI had 37 percent lower verbal memory scores and 18 percent lower levels of SERT in the hippocampus than healthy controls.

The team is currently investigating whether PET imaging of serotonin could be a marker to detect the progression of the disease, either alone or in conjunction with scans that detect amyloid.

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