- Elevated levels of amyloid-beta and tau proteins are known to be
associated with an increased risk of Alzheimer's disease, a form of
- Study shows that chronic sleep deprived persons also show elevated
levels of beta-amyloid and tau proteins with possibly higher risk of
developing Alzheimer's disease.
Regular disruption of a
good night's sleep, especially slow wave sleep in otherwise healthy middle aged
adults might put them at an increased risk of Alzheimer's disease (AD) later in
life, according to a recent study conducted by Washington University School of Medicine
in St. Louis, Radboud University Medical Centre in the Netherlands, and
findings of the study appeared in the journal Brain
‘Disruption of slow wave sleep is associated with elevated levels of beta-amyloid and tau proteins which are known to be associated with Alzheimer’s disease.’
Poor Sleep And Cognitive Impairment - Possible Link To Alzheimer's
Previous research by Holtzman, co-first
author Yo-El Ju, MD, an assistant professor of neurology, and others have shown
that persons with
chronic sleep problems, like sleep apnea develop
cognitive impairment significantly earlier compared to good sleepers
one of the earliest signs of Alzheimer's disease
, a neurodegenerative condition is impaired cognition.
on the association between poor sleep and cognitive impairment, the study team
wanted to carry the research forward and determine
the reason for cognitive impairment in persons with chronic
poor sleep and whether this could be a possible piece in the puzzle
think that perhaps chronic poor sleep during middle age may increase the risk
of Alzheimer's later in life", says Holtzman.
Finding the Reason for Brain Damage in
Sleep Deprived Persons
order to get to the bottom of the matter, the team comprising of Holtzman; Ju;
co-first author and graduate student Sharon Ooms of Radboud; Jurgen Claassen,
MD, PhD, of Radboud; Emmanuel Mignot, MD, PhD, of Stanford; and colleagues
studied 17 healthy adults aged between
35 to 65
with no sleep problems or cognitive issues.
- Initially, each participant was
given an activity monitor to wear that tracked how much they slept at
night for a period of five days
- Following this, each volunteer came
to the School of Medicine to a specially designed Sleep Room, the perfect
place for a night's rest - dark, soundproofed and climate controlled and
just large enough for one person.
- Here, they were fitted with
headphones and electrodes on the scalp to monitor brain activity and wave
- Half the participants were randomly
chosen to have their sleep disturbed during the night they spent in the
Sleep Room. Whenever the participants drifted into slow wave pattern deep
sleep, they were disturbed by a series of beeps via their headphones,
getting louder until their deep sleep was disturbed and they entered
- The next morning, the persons whose slow wave sleep had been
disturbed reported feeling tired and lethargic although they had slept the
entire time and could not recollect being woken up.
- All the participants underwent a spinal tap to measure levels of
amyloid-beta and tau proteins (known to be elevated in AD) in their
cerebrospinal fluid (CSF).
- The same process was repeated a month letter. Only, this time the
roles were reversed and the persons who were disturbed during their sleep
earlier were now allowed to sleep uninterrupted and vice versa. Again, a spinal tap was performed to
measure the levels of the beta-amyloid and tau proteins.
- The study team compared the levels of amyloid-beta and tau proteins
in the participants on the night the sleep was interrupted and the night
they slept without any disturbances in the Sleep room.
- Following a single night interrupted sleep there was a ten percent
increase in beta-amyloid levels but tau protein remained unchanged.
- However, the individuals who had slept poorly at home during
monitoring of sleep through activity monitor showed a rise in tau protein
were not surprised to find that tau levels didn't budge after just one night of
disrupted sleep while amyloid levels did, because amyloid levels normally
change more quickly than tau levels," Ju said. "But we could see,
when the participants had several bad nights in a row at home, that their tau
levels had risen."
Disrupted Slow Wave Sleep can Cause Brain Damage
It is during the deep sleep
(slow wave sleep) that the
nerve cells rest and the accumulated
toxic metabolites and products
during the day when the brain is constantly
thinking and functioning are cleared by
the cell scavenging mechanisms
Therefore, disturbed slow wave sleep interferes with cell scavenging and clearing
and allows accumulation of harmful proteins such as tau and beta-amyloid that
can cause nerve cell damage and death.
This may not be of consequence if sleep is
in this case the elevated proteins will return to
baseline levels when proper sleep is restored. The danger is in those with
chronic sleep deprivation.
main concern is people who have chronic sleep problems," Ju said. "I
think that may lead to chronically elevated amyloid levels, which animal
studies have shown lead to increased risk of amyloid plaques and
Disease in Brief
Alzheimer's disease is a
that often is seen in the elderly, characterized by loss of memory and impaired cognition
that worsens over time and leaves the person totally dependent on a carer
for all activities of daily living.
there are over 5 million Americans living with Alzheimer's disease and until
now there is no treatment
to slow or
prevent progression of the disease.
The brains of persons
with Alzheimer's disease have been shown to contain amyloid plaques
(amyloid-beta protein) and tangles of tau protein
conclusion this study does not aim to establish a causal relationship between
poor sleep and Alzheimer's disease. It suggests that poor sleep is associated
with accumulation of certain toxic proteins occurring in AD, that can be
prevented by a refreshing and fitful night's rest.
the words of Ju, co-first author, "At this point, we can't say whether
improving sleep will reduce your risk of developing Alzheimer's. All we can
really say is that bad sleep increases levels of some proteins that are
associated with Alzheimer's disease. But a good night's sleep is something you
want to be striving for anyway."
- David M. Holtzman et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain, July 2017 DOI: 10.1093/brain/awx148