Health

Acute Sleep Loss Increases Blood Levels of Alzheimer’s Biomarker

SAN ANTONIO — Acute sleep loss results in increased plasma levels of tau, which has been proposed as a biomarker to assess subsequent risk of Alzheimer‘s disease (AD), new research suggests.

This may be because of “increased neuronal activity that’s required to sustain wakefulness during the night,” said study investigator Jonathan Cedernaes, MD, PhD, from the Department of Medical Sciences at Uppsala University in Sweden.

The findings were presented here at a late-breaking abstract session at SLEEP 2019: 33rd Annual Meeting of the Associated Professional Sleep Societies.

Sleep Loss Harms the Brain

Research has shown that insufficient sleep has harmful effects on the brain. In a prior study, Cedernaes and colleagues found that sleep disturbances were associated with an increased risk of developing dementia in initially cognitively healthy men during a 40-year observation period.

The association was strongest for AD. Disrupted sleep has also been shown to increase cerebrospinal fluid (CSF) levels of amyloid beta and tau.

The aim of the current study was to see whether acute sleep loss alters diurnal levels of plasma-based biomarkers that are associated with AD.

Using a within-subject, crossover design, 15 healthy young men participated in 2 standardized in-lab sessions with two different conditions — one night of normal sleep and one night of overnight sleep deprivation.

Levels of total tau and neurofilament light chain (NfL) were analyzed using ultrasensitive assays in plasma samples obtained in the evening prior to, and in the morning after, each intervention.

“We noted an evening to morning increase in plasma levels of total tau following the acute sleep loss condition, while levels of total tau decreased in the normal sleep condition, such that there was a significant change in the evening to morning levels between these two conditions,” Cedernaes said during his presentation.

However, no differences were found between the two conditions for the evening to morning change in plasma NfL levels.  NfL is a marker of neuroaxonal damage. The finding that levels of NfL did not change as a result of acute sleep loss argues against acute neuroaxonal injury, and may instead be due to sustained neuronal activity during overnight wakefulness, Cedernaes said.

Future studies are warranted to assess circadian modulation of these biomarkers, whether they are long-lasting, and the interplay with other lifestyle factors, he noted.

Additional Evidence

Commenting on the findings for Medscape Medical News, Andrew Varga, MD, assistant professor of medicine, pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai in New York City, said the study was interesting for a number of reasons.

“While there was some previous evidence that various forms of sleep disruption could impact tau and its phosphorylation, it also remained unclear how quickly this could happen. The work from this abstract suggests that increases in plasma tau can be seen in just one night of overnight sleep loss,” said Varga, who was not involved in the research.

“Though it’s a bit of a leap, taken together, it adds to evidence that sleep loss can increase AD risk,” he added. “The fact that NfL was not elevated suggests that the effect of one night of sleep loss is less likely to be due to damage to neurons, but may be the consequence of increased neural activity leading to increased tau production.”

The study was supported by the Swedish Society for Medical Research, the Swedish Brain Foundation, the Åke Wiberg Foundation, the Knut and Alice Wallenberg Foundation, the NovoNordisk Foundation, Bissen Brainwalk, the Swedish Alzheimer Foundation, and the Swedish state. Cedernaes and Varga have disclosed no relevant financial relationships.

SLEEP 2019: 33rd Annual Meeting of the Associated Professional Sleep Societies: Abstract LBA2. Presented June 10, 2019.

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