Alzheimer’s: Sleeping pill suvorexant may reduce toxic protein buildup

• About 32 million people around the world have Alzheimer’s disease.
• Most scientists believe Alzheimer’s disease is caused by a buildup of amyloid and tau proteins in the brain.
• Researchers from the Washington University School of Medicine in St. Louis have found people in a small study who took an insomnia medication experienced a drop in both Alzheimer’s-related proteins.

The buildup of beta-amyloid and tau proteins in the brain is currently considered the main cause of Alzheimer’s disease — a type of dementia affecting about 32 million people globally.

Now researchers from the Washington University School of Medicine in St. Louis, MO have found in a small study that people who took the insomnia medication suvorexant experienced a drop in both Alzheimer’s-related proteins.

The study was recently published in the journal Annals of Neurology.

What are beta-amyloid and tau proteins?

Beta-amyloid forms when a larger protein found in neurons called amyloid precursor protein (APP) breaks down.

Beta-amyloid is known to be chemically “stickier” than other parts of APP, causing the beta-amyloid fragments to clump together. This forms amyloid plaques inside the brain, making it harder for neurons to talk to each other.

Tau protein is also found in neurons. When a person has Alzheimer’s disease, the tau proteins can act abnormally, causing them to stick to each other.

This causes what is known as tau tangles inside neurons. The tau tangles interfere with a neuron’s ability to make and recycle proteins, eventually killing the cell.

How sleep issues affect Alzheimer’s disease

Medical News Today spoke with Dr. Brendan Lucey, an associate professor of neurology and director of the Sleep Medicine Center at Washington University School of Medicine in St. Louis and first author of this study.

Dr. Lucey said sleep and Alzheimer’s disease are hypothesized to have a bi-directional relationship:

“Sleep disturbances are a risk factor for Alzheimer’s disease and the changes in the brain associated with Alzheimer’s disease are associated with sleep disturbances.”

A 2018 study found sleep deprivation led to increased beta-amyloid protein. And a study in 2021 found people who slept six hours or less in middle age were more likely to develop dementia later in life.

Dr. Lucey and his research team have also previously published research showing a link between chronic poor sleep and increased beta-amyloid proteins. And another study linked higher levels of tau protein to decreased deep sleep.

Additionally, researchers have found sleep issues to be typical symptoms of Alzheimer’s disease.

“This raises the possibility of monitoring sleep as a marker for Alzheimer’s disease risk and — as with this study — using a sleep intervention to delay/prevent Alzheimer’s disease,” Dr. Lucey added.

How orexin affects cognitive function

Dr. Lucey said the idea for this trial came from previous work showing that a dual orexin receptor antagonist decreased both soluble amyloid-beta levels and amyloid pathology in a mouse model.

“This study was conceived as the first direct translation of that finding using the first FDA-approved dual orexin receptor antagonist, suvorexant,” he added.

Orexin is a natural biomolecule that promotes wakefulness. The orexin receptor system plays an important role in a number of natural processes, including the sleep-wake cycle, feeding behavior, cognition, and mood.

Previous studies have linked orexin as a potential therapeutic target for Alzheimer’s disease, finding it is dysregulated in people with the disease.

And other research has found blocking orexin activation helps prevent stress-induced memory issues.

Findings on suvorexant for brain health

For this study, Dr. Lucey and his team administered the insomnia drug suvorexant to some of the study participants. There were 38 participants in total, all between the ages of 45 and 65 with no signs of cognitive impairment.

For two nights, study participants were either given a low 10mg dose, a higher 20mg dose, or a placebo.

Using cerebrospinal fluid collected via a spinal tap every two hours, researchers found the amount of amyloid protein dropped 10% to 20% in the cerebrospinal fluid of people receiving the high dose of suvorexant compared to people who had received a placebo.

Additionally, those receiving the higher dose of suvorexant saw a 10% to 15% drop in the amount of hyperphosphorylated tau protein in their cerebrospinal fluid, compared to people who received the placebo.

“We hypothesized that amyloid-beta would decrease,” Dr. Lucey commented. “The p-tau findings were surprising to me. I was also surprised by how long into the day amyloid-beta and pT181 remained lower.”

Next steps in Alzheimer’s research

Dr. Lucey is quick to point out that this study does not support using suvorexant and dual orexin receptor antagonists to prevent or delay Alzheimer’s disease, nor does it support or justify additional studies giving the drug for longer periods and to test that it prevents/delays Alzheimer’s disease symptoms.

“Suvorexant is approved for treatment of insomnia, including in mild-to-moderate Alzheimer’s disease patients,” he continued. “Patients should discuss with their doctors if suvorexant and other dual orexin receptor antagonists are an option to treat their insomnia.”

As for the next steps in this research, Dr. Lucey said he has clinical trials enrolling participants without problems with thinking and memory, but who have amyloid in their brains.

“Participants will receive dual orexin receptor antagonists for months and we will follow Alzheimer’s proteins like amyloid and tau,” he explained. “These studies will test if chronic administration of these drugs lowers Alzheimer biomarkers over longer periods of time.”

Treating sleep disorders to slow cognitive decline

MNT also spoke with Dr. Karen D. Sullivan, a board certified neuropsychologist and creator of the I CARE FOR YOUR BRAIN education program, about this study.

She said as this is a small, proof-of-concept study, it would not impact how she talks to her people at high risk for Alzheimer’s disease about sleep issues:

“I would continue to talk to them about the vital importance of long periods of continuous sleep to optimize the immune-mediated ‘cleaning out process’ that happens during deep sleep. Identifying and treating sleep disorders remains one of our most evidence-based ways of reducing risk and impact of most dementias.”

“Meta-analysis have shown that there are numerous sleep changes that happen in Alzheimer’s that are correlated with worsening cognition,” she continued. “These include reductions in sleep efficacy, less total sleep time most importantly in REM stages, and increased awakenings. Many of these can be improved with sleep hygiene interventions, identifying and treating co-existing sleep disorders, light therapy, and low dose melatonin.”

“I would like the authors to explain the mechanism of action and how their analysis fits in with the larger literature on amyloid and cerebrospinal fluid as a biomarker in Alzheimer’s disease,” Dr. Sullivan added.

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