An antidepressant may slow plaque growth associated with Alzheimer’s disease.
What would you do with a 15-year window between the diagnosis and the onset of a terminal illness? Most likely, everything possible to slow the progress of the disease.
With Alzheimer’s disease (AD), there is on average a 15-year gap between the development of amyloid plaques in the brain and the presentation of symptoms. But researchers at the University of Pennsylvania believe they may have found a drug treatment that prevents amyloid formation, which could slow AD onset.
Amyloid plaques are caused by a build-up of the amyloid-beta (Aβ) peptide in the brain and are thought to be a trigger for AD. All of us, even the young and healthy, have Aβ in their brain along with spinal fluid. We get into trouble when there is too much build up over too long a period of time.
Amyloid plaques and neurofibrillary tangles are characteristic of AD, an illness that affects more than five million Americans, according to the Alzheimer’s Association. AD is the most common form of dementia, and is associated with the loss of brain function, memory, and motor skills.
Antidepressant medications are used to boost levels of the neurotransmitter serotonin. In a report published in
The formula is simple: more serotonin means less Aβ. Researchers focused on selective serotonin reuptake inhibitor (SSRI) drugs, which block the absorption of serotonin that the brain releases naturally, increasing the amount of serotonin that’s available. Specifically, researchers focused on the effects of the drug citalopram in mouse studies.
In these mouse models of AD, citalopram stopped the growth of amyloid plaques and reduced the formation of new plaques by 78 percent. “We used citalopram because it is one of the most selective SSRIs—but all the SSRIs we’ve tested so far in mouse models work to lower amyloid concentrations,” says study co-author Dr. Yvette Sheline, a professor of psychiatry at the University of Pennsylvania’s Perelman School of Medicine.
In addition to mouse studies, Sheline and her team found that citalopram lowered levels of Aβ in the cerebrospinal fluid (CSF) of young and healthy humans by 37 percent, compared to a group of healthy human volunteers who took a placebo pill.
While moving from mouse models to human testing will require clearing some high hurdles, it’s possible that antidepressants or another form of SSRI drugs will be used to slow AD onset in the future.
“We still have more work to do before prevention trials could be undertaken,” Sheline says. “The next step we will take—we are starting this study momentarily—is to enroll older cognitively normal volunteers to have their CSF tested for amyloid concentration before and after taking [an] SSRI or placebo for two weeks. This will enable us to determine if the drug effect is sustained.”
“If that trial is successful then we will plan a prevention trial where we use [an] SSRI to treat cognitively normal elderly [people] at risk for AD and where we hope to show that giving [an] SSRI for several years prevents brain plaque growth,” Sheline adds.
Stopping AD before it starts? Suffice it to say that using an already approved SSRI to prevent AD in elderly patients would be tremendous step forward.