Could a commonly prescribed antidepressant slow onset of Alzheimer's?
Thursday 15 May 2014 - 8am PST
New research from the Washington University School of Medicine ∈St. Louis, MO, and the University of Pennsylvania finds that a commonly prescribed antidepressant may be effective at slowing onset of Alzheimer's disease.
The problems with memory and cognition caused by Alzheimer's are strongly influenced by a build-up of plaques ∈ the brain. The plaques consist of amyloid beta - a protein that is produced as part of normal brain activity. Patients with Alzheimer's disease, however, have elevated levels of amyloid beta, which results ∈ the protein clumping together as plaques.
A previous study by senior author John Cirrito, PhD, assistant professor of neurology at Washington University, suggested that the production of amyloid beta can be reduced by the chemical messenger serotonin.
Most antidepressants work by stimulating the flow of serotonin ∈ the brain, which prompted Cirrito and first author Dr. Yvette Sheline to investigate antidepressants as a tool to control amyloid beta production.
As part of a 2011 study, they tested a range of antidepressants ∈ mice genetically altered to develop Alzheimer's as they age. The mice ∈ the trial were young and had not yet developed the brain plaques that characterize the disease. The researchers found that the antidepressants successfully reduced amyloid beta production ∈ the mice by an average of 25% after 24 hours.
In their new study - published ∈ the journal Science Translational Medicine - the researchers administered the antidepressant citalopram to older mice who already had plaques ∈ their brain. They then tracked the growth of plaques ∈ the mice for 28 days using a technique called "two-photon imaging."
They found that citalopram halted the growth of the existing plaques, while formation of new plaques was reduced by 78%.
In a second phase of the experiment, 23 human subjects between the ages of 18 and 50 received a single dose of citalopram. The participants were not cognitively impaired or depressed. Over the 24 hours following the administration of the citalopram, samples of spinal fluid were taken from the participants.
The spinal fluid samples showed that amyloid beta production had dropped ∈ the human participants by 37%.
"Antidepressants appear to be significantly reducing amyloid beta production, and that's exciting," says Cirrito.
'There is still much more work to do'
"But while antidepressants generally are well tolerated," he continues, "they have risks and side effects. Until we can more definitively prove that these drugs help slow or stop Alzheimer's∈ humans, the risks aren't worth it. There is still much more work to do."
The next step for the team is to use mouse models again ∈ an attempt to understand the molecular process that causes serotonin to halt the production of amyloid beta.
Dr. Sheline says the team also plans to study older adults who will be treated for 2 weeks with antidepressants.
"If we see a drop ∈ levels of amyloid beta ∈ their spinal fluid after 2 weeks," she explains, "then we will know that this beneficial reduction ∈ amyloid beta is sustainable."
Last year, a study published ∈JAMA suggested that poor sleep quality may contribute to an increased build-up of amyloid beta plaques ∈ the brains of older people. Meanwhile, a study published around the same time ∈ the journal Neurology found an association between hardening of the arteries and the build-up of amyloid beta plaques ∈ the brain.
Written by David McNamee http://www.medicalnewstoday.com/articles/276838.php (Accessed May 16, 2014)
The first tests of this new research were made
