Acute Sleep Loss Triggers Increase in Plasma Levels of Tau Protein in Young Adults

A team of Swedish researchers has found that acute sleep loss results in increased blood levels of t-tau protein, a key biomarker for nervous system disorders such as Alzheimer’s disease.

Previous studies had shown that disrupted sleep increased CSF (cerebrospinal fluid) levels of tau and beta-amyloid (ABeta) and was associated with an increased risk of Alzheimer’s disease (AD). The aim of the current study, conducted by investigators at Uppsala University (Sweden), was to determine whether acute sleep loss altered diurnal profiles of plasma-based AD-associated biomarkers.

The current study involved 15 healthy, normal-weight men with an average age of 22 years. The design of the experiment comprised two phases. For each phase, the subjects were housed in a sleep clinic for two days and nights under a strict meal and activity schedule. Blood samples were collected in the evening and again in the morning. For one phase, participants were allowed an uninterrupted night of sleep both nights. For the other phase, participants were allowed uninterrupted sleep the first night followed by a second night of sleep deprivation.

Plasma levels of total tau (t-tau), ABeta40, ABeta42, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in the blood samples were assessed using ultrasensitive single molecule array assays or ELISAs,

Results revealed the after sleep deprivation, the subjects had an average 17% increase in tau levels in their blood. In contrast, following a night of interrupted sleep, the subjects had an average increase in tau levels of only 2%. No changes between the sleep conditions were seen for levels of ABeta40, ABeta42, NfL, or GFAP.

"Many of us experience sleep deprivation at some point in our lives due to jet lag, pulling an all-nighter to complete a project, or because of shift work, working overnights. or inconsistent hours," said senior author Dr. Jonathan Cedernaes, a senior researcher at Uppsala University. "Our exploratory study shows that even in young, healthy individuals, missing one night of sleep results in a slight increase in the level of tau in blood. This suggests that over time, similar types of sleep disruption could potentially have detrimental effects."

"It is important to note that while accumulation of tau in the brain is not good, in the context of sleep loss, we do not know what higher levels of tau in blood represent" said Dr. Cedernaes. "When neurons are active, release of tau in the brain is increased. Higher levels in the blood may reflect that these tau proteins are being cleared from the brain or they may reflect an overall elevation of the concentration of tau levels in the brain. Future studies are needed to investigate this further, as well as to determine how long these changes in tau last, and to determine whether changes in tau in blood reflects a mechanism by which recurrent exposure to restricted, disrupted or irregular sleep may increase the risk of dementia. Such studies could provide key insight into whether interventions targeting sleep should begin at an early age to reduce a person's risk of developing dementia or Alzheimer's disease."

The study was published in the January 8, 2020, online edition of the journal Neurology.

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