Antidepressants show signs of countering Alzheimer’s

Serotonin reuptake inhibitors may reduce brain plaques associated with Alzheimer’s disease. Read More

Widely used antidepressants may reduce the ominous brain plaques associated with Alzheimer’s disease, a new study in mice and humans finds.

Brain scans of people who have taken antidepressants reveal fewer clumps of the protein amyloid-beta, a target of Alzheimer’s prevention strategies, when compared with people who have not taken the drugs.

Many in the field voiced caution about the results. But if borne out by further study, the findings may point to a new, relatively safe way to treat and prevent Alzheimer’s disease, which is the sixth leading cause of death in the United States.

In the study, mice genetically engineered to overproduce amyloid-beta, or A-beta, were given one of three selective serotonin reuptake inhibitors, a class of antidepressants that boost circulating levels of the chemical messenger serotonin in the brain. After a single dose of the antidepressants, A-beta levels dropped in the fluid that surrounds mouse brain cells, researchers report online the week of August 22 in the Proceedings of the National Academy of Sciences. A full day after receiving the drug, the mice’s A-beta levels fell by nearly a quarter.

Long-term, chronic administration of the drug had a larger effect. Engineered mice that took the SSRI citalopram for four months had about half the A-beta plaques in their brains as mice that hadn’t had the drug. This reduction seems to happen through a protein called ERK, which serves as the middleman between brain cells’ serotonin-sensing proteins and A-beta production.

Figuring out the details of this process may open the door for developing new ways to prevent A-beta buildup, says study coauthor John Cirrito of the Washington University School of Medicine in St. Louis.

To see if a similar effect might be happening in people, the scientists scanned the brains of 186 cognitively normal elderly people and looked for signs of A-beta plaques. The team used a compound called PIB that binds to big clumps of A-beta in the brain and glows on a PET scan.

Of these participants, 52 reported that they had taken an antidepressant in the last five years. These people, researchers found, had about half the A-beta load in their brains as the people who hadn’t taken an antidepressant. What’s more, the length of time the participants took the drugs correlated with the density of A-beta plaques in the brain — the longer the antidepressant dose, the less plaque.

“We think there are influences going in two opposite directions,” says study coauthor and psychiatrist Yvette Sheline, also of Washington University. “We think depression pushes you toward dementia, but antidepressant treatment pushes you toward protection.”

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Posted on November 2, 2011
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