Preventing Alzheimer’s Disease, With An Antidepressant

Preventing Alzheimer’s Disease, With An Antidepressant

By Melissa Healy, Los Angeles Times

Citalopram, an antidepressant better known by its commercial name Celexa, has a remarkable side effect, a new study has found: In both mice bred to develop Alzheimer’s disease and in healthy human volunteers, the selective serotonin reuptake inhibitor, or SSRI, drives down the production of a protein called beta-amyloid, which in the brains of those with Alzheimer’s clumps together in sticky plaques and is thought to short-circuit the brain’s wiring.

In study participants free of Alzheimer’s disease or any other neuropsychiatric affliction, citalopram was found to reduce the concentration of beta-amyloid in the cerebrospinal fluid (outside of the brain) by 38 percent. Researchers see that as a clear sign that beta-amyloid protein in the brain, too, declines in those taking the antidepressant.

In older mice bred to develop an animal version of Alzheimer’s disease, a 28-day regimen of citalopram arrested the growth of beta-amyloid plaques and reduced the appearance of new plaques by 78 percent. In healthy volunteers, the slowdown in beta-amyloid protein production, as measured in cerebrospinal fluid by lumbar puncture, was virtually immediate, occurring within hours of their having receive two doses of citalopram at 30 milligrams each.

The new research, published Wednesday in the journal Science Translational Medicine, suggests that the widely-used antidepressant — and possibly several others in the same class — could become a relatively simple, cheap and potentially powerful way to prevent or delay the onset of Alzheimer’s when taken by those at greatest risk of developing the devastating dementia.

That promising news could not come at a more opportune time. In their wide-ranging research on Alzheimer’s disease, scientists have made enormous strides in devising means to detect and diagnose Alzheimer’s in its earliest stages. But they’ve had far less success in developing therapies to thwart the disease before its symptoms of memory loss and confusion become evident.

The result of that mismatch is that many of those at greatest risk of developing Alzheimer’s dementia feel they have little to gain from early screening for the disease. They would live with the knowledge that the disease would rob them of memory, independence and even a sense of self. But they could do nothing to avert that outcome.

But Alzheimer’s specialist Dr. Lon Schneider of the University of Southern California says it’s far too early for people fearing a future marred by the disease to start taking citalopram, particularly at the dosage levels shown to be effective in the current study. For starters, he noted, the success of antidepressants in preventing Alzheimer’s disease rests on an assumption that has not always panned out in research: that reducing beta-amyloid in the brain will change the course of the illness.

Beyond that, Schneider cautioned that an article published two months ago on citalopram as treatment for agitation associated with Alzheimer’s found further cognitive impairment and cardiac toxicity in those taking it. The maximum dose used in the current study — the equivalent of 60 milligrams — is three times higher than the highest dose recommended for those over 60, he added.

“People should not start popping citalopram or other antidepressants in the expectation that they will prevent Alzheimer’s disease,” said Schneider, who was not involved in the latest study. “They could be doing some substantial harm.”

In the study, researchers from University of Pennsylvania in Philadelphia and Washington University Medical School in St. Louis set out to explore the untapped powers of SSRIs to reduce production of beta-amyloid. Past research has found that while SSRIs do little to improve the clearance of beta-amyloid protein from the brain, they do reduce the protein’s production in the brain.

Studies tracking the progression of Alzheimer’s disease have suggested that years and even decades before symptoms appear, beta-amyloid proteins become more plentiful in the brain (and spill into cerebrospinal fluid where they are more easily measured). First, the proteins aggregate in a sort of soluble goo form, and with time, they turn into insoluble, hard plaques. Both can disrupt signals among brain cells, but as plaques proliferate, normal communication among neurons is completely broken, and dementia takes hold.

That conversion from goo to gunk appears to accelerate when beta-amyloid proteins become more concentrated, said the researchers. Thus, in theory, a medication that can keep concentrations of beta-amyloid low might prevent amyloid plaques from forming altogether.

Citing their own past research, the authors of the article suggested the same effect seems to take place with a wide range of SSRIs. In the current study, the suppression of beta-amyloid production was not only substantial but it could also be detected very rapidly, in as few as five minutes after the drug was taken by healthy human volunteers.

The researchers found the suppression of beta-amyloid production to be greater at larger doses of citalopram, but the most effective dose tested on mice was comparable to a 50-milligram dose of citalopram, a dose that is substantially higher than that commonly used to treat those with depression.

Photo: Me via Flickr
want more health news? Sign up for our daily email newsletter!

Start your day with National Memo Newsletter

Know first.

The opinions that matter. Delivered to your inbox every morning

Former President Donald Trump

Former President Donald Trump

Former President Donald Trump's Truth Social platform is set for its initial public offering (IPO) as soon as next week after its merger was approved by a special purpose acquisition company. But while Trump himself stands to reap a multibillion-dollar windfall, investors may not be as lucky given Trump's past IPO record.

Keep reading...Show less
Leonard Leo
Leonard Leo

GOP activist Leonard Leo is co-chair of the influential Federalist Society, which has produced all six of the Supreme Court of the United States' (SCOTUS) conservative jurists — including Chief Justice John Roberts. And ever since the office of Washington, DC Attorney General Brian Schwalb started investigating the Federalist Society for alleged violations of its nonprofit status, Leo's allies have been attacking him every step of the way.

Keep reading...Show less
{{ post.roar_specific_data.api_data.analytics }}