Could Aspirin Help Prevent Alzheimer’s Disease?

February 11, 2019

Can an aspirin a day keep Alzheimer’s away? If only it were that simple. However, new research suggests that there does seem to be some hope that aspirin, one of the most widely used drugs in the world, may help treat some aspects of this devastating brain disorder.

Scientists have found that aspirin works with certain sub-cellular mechanisms in the brain to prevent the accumulation of amyloid plaques, the sticky protein clumps around brain cells thought to be the main cause of Alzheimer’s disease, according to this new study done in mice.

In the study, the mice experimented with aspirin found that aspirin enhanced the ability of lysosomes, which act somewhat like cellular waste handlers and recyclers, to remove amyloid plaque or prevent it from forming in the first place. Aspirin should have the same effect on the human form of Alzheimer’s disease, too, say researchers, who published their findings today (June 2) in the journal Neuroscience.

Alzheimer’s disease, the most common type of dementia, is a progressive brain disease that affects nearly 6 million Americans and is the sixth leading cause of death for all U.S. adults, according to the Centers for Disease Control and Prevention. There is no cure, and the drug has had very limited success in slowing the disease’s progression.

Aspirin, also known as acetylsalicylic acid, is an inexpensive drug with a century-long history and is safe in low doses, except for a small risk of possible stomach irritation and internal bleeding. Many adults take low doses of aspirin daily as a mild blood thinner to help prevent heart attacks.

In fact, several population-wide studies of aspirin and heart health have found that aspirin may also reduce the risk of Alzheimer’s disease, albeit modestly. A meta-analysis by Chinese researchers published in March 2018 in Frontiers in the Neuroscience of Aging reviewed 18 whole-population studies and found that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, was associated with an average 20% reduction in the risk of developing Alzheimer’s disease.

Aspirin and Alzheimer’s disease
Researchers at Rush University Medical Center in Chicago, building on a possible link between aspirin and Alzheimer’s prevention first observed more than a decade ago, have crafted experiments that involve giving aspirin to mice with a mouse version of Alzheimer’s disease, as well as applying aspirin directly to mouse brain cells grown in the lab.

Both approaches – in vivo and in vitro – appear to prevent or reverse the biological symptoms of Alzheimer’s disease, said Kalipada Pahan, lead study author and professor of neuroscience at Rush University.

Pahan explained that aspirin activates a cellular receptor called PPARα, which in turn regulates a protein called TFEB, a so-called master regulator of lysosomal activity. In short, aspirin helps cells remove cellular debris, including proteins that form amyloid plaques.

“We expect to see similar results in human brain cells,” Pahan told Live Science.

In fact, other drugs, such as the triglyceride-lowering drug gemfibrozil (sold as Lopid), also target TFEB, Pahan said, but aspirin is safe enough to use without a prescription and has fewer side effects.

Rajini Rao, a professor of physiology at the Johns Hopkins University School of Medicine in Baltimore who was not involved in the study, said the new study “provides an elegant mechanistic explanation for the protective effects of aspirin seen at the cellular and model animal level.”

However, she noted that it’s unclear from the study whether the improved amyloid clearance translates into better brain function.

“The results of epidemiological studies on aspirin use and dementia are mixed,” Rao told Live Science. “While there are some indications of protection, other studies have failed to replicate this. Unfortunately, this is true of almost all drugs used in Alzheimer’s trials – more than 99 percent have failed in the clinic – which is why Alzheimer’s research is particularly challenging.”

Pahan said that while aspirin is relatively safe, it does carry some risks when used on a daily basis and should not be used liberally as an unproven method of treating or preventing Alzheimer’s disease. He added that for aspirin to stimulate lysosomal activity, the cellular receptor PPARα needs to be present, so any person with Alzheimer’s disease who lacks a sufficient number of PPARα receptors will not benefit from aspirin. Pahan said this may account for the mixed results of population-wide studies.