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Sleep to Clean: A Prevention of Plaques That Lead to Alzheimer’s Disease

Describes how a lack of sleep can actually increase  the risk of Alzheimers which results in a lack of ability to remember. States that with sleep there is a lower production of a certain protein that is linked with Alzheimers disease. This links the correlation between a lack of sleep and lowered cognitive function as "the rapid rate of amyloid-beta production causes the proteins to clump up into plaque. This unsettling change results in brain dysfunction; proteins like tau create neurofibrillary tangles that choke off the insides of neurons."

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Take a look inside the structure of a healthy brain. As they are created and destroyed, billions of neurons reside and correspond with each other through synapses. As new experiences feed into our brain every second, the synapses receive neurotransmitters that are responsible for the communication in our brain: seeing, thinking, remembering. However, in the brain of an Alzheimer's patient, harmful proteins called amyloid-beta 42 block these synapses. Naturally produced by neurons, amyloid-beta proteins accumulate and lead to Alzheimer's if not cleaned out fast enough by microglia cells, the cleaners for the brain. Over time, the rapid rate of amyloid-beta production causes the proteins to clump up into plaque. This unsettling change results in brain dysfunction; proteins like tau create neurofibrillary tangles that choke off the insides of neurons. Now, the once messy room is structurally and functionally destroyed by a hurricane. Looking to rapidly fix the chaos, microglia cells secrete inflammatory factors, resulting in prolonged inflammation and even the destruction of neurons.

In the past years, scientists began noticing a relationship between Alzheimer's disease and sleep. Dr. Yo-El Ju evaluated patients in sleep apnea treatment. Following their successful treatment, she found that both the production and number of beta-amyloids had decreased. Laura Lewis, an assistant professor from Boston University who conducted a study on brain waves and sleep, said that the patients seemed "to have a change in their ability to clear proteins or waste products from their brain." Hence, sleep has a vital role in the reduction of beta-amyloid plaques - the emerging signs of oncoming Alzheimer's.

But, how come? In a separate study done by Dr. Maiken Nedergaard, it was discovered that the brain cleans waste two times faster when asleep. "So things like amyloid-beta, which are implicated in Alzheimer's disease, seem to actually be removed more rapidly from the brain," Dr. Lewis pointed out. Allowing microglia cells and other proteins to actively sweep out waste at much faster rates, sleep reshapes the untidy room in the brain, solidifying memories. With a healthy sleep routine, the fate of our brains could be deterred from Alzheimer's disease.

There is still much to discover. As Dr. Lewis said, "I don't know whether it's that sleep increases clearance or whether sleep decreases the production of waste products." Every step in the understanding of neurology can help uncover new preventions for Alzheimer's, improving brain health for generations to come.
Works Cited
Alzheimer's Association. " Alzheimer's Facts and Figures." Alzheimer's Association." Alzheimer's Association.

Cunningham, Aimee. " Lack of Sleep Is Tied to Increases in Two Alzheimer's Proteins." Science News, 24 Jan. 2019.

Hamilton, Jon. " Deep Sleep Protects against Alzheimer's, Growing Evidence Shows. " NPR, 17 Nov. 2020.

Konnikova, Maria. " Goodnight. Sleep Clean. " The New York Times, 11 Jan. 2014.

" What Happens to the Brain in Alzheimer's Disease? " National Institute on Aging, 16 May 2017.

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Sleep to Clean: A Prevention of Plaques That Lead to Alzheimer's Disease

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Take a look inside the structure of a healthy brain. As they are created and destroyed, billions of neurons reside and correspond with each other through synapses. As new experiences feed into our brain every second, the synapses receive neurotransmitters that are responsible for the communication in our brain: seeing, thinking, remembering.

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After 10-Year Search, Scientists Find Second ‘Short Sleep’ Gene

Describes people known as short sleepers. These are people who are able to sleep about 4-6 hours which is less than the average recommended amount of time which 7-9 hours. This is astonishing because they are able to function of full capabilities with only 4-6 hours of sleep. This contradicts the claim that sleep is needed to improve cognitive function since it doesn't apply to everyone. "Their efforts uncovered a single-letter mutation in a gene known as ADRB1 that, like the mutation in DEC2, was associated with natural short sleep".

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After 10-Year Search, Scientists Find Second 'Short Sleep' Gene | UC San Francisco

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After a decade of searching, the UC San Francisco scientists who identified the only human gene known to promote "natural short sleep" - lifelong, nightly sleep that lasts just four to six hours yet leaves individuals feeling fully rested - have discovered a second.

"Before we identified the first short-sleep gene, people really weren't thinking about sleep duration in genetic terms," said Ying-Hui Fu, PhD, professor of neurology and a member of the UCSF Weill Institute for Neurosciences. Fu led the research teams that discovered both short sleep genes, the newest of which is described in a paper published Aug. 28, 2019, in the journal .

According to Fu, many scientists once thought that certain sleep behaviors couldn't be studied genetically. "Sleep can be difficult to study using the tools of human genetics because people use alarms, coffee and pills to alter their natural sleep cycles," she said. These sleep disruptors, the thinking went, made it difficult for researchers to distinguish between people who naturally sleep for less than six hours and those who do so only with the aid of an artificial stimulant.

Natural short sleepers remained a mystery until 2009, when a study conducted by Fu's team discovered that people who had inherited a particular mutation in a gene called DEC2 averaged only 6.25 hours of sleep per night; study participants lacking the mutation averaged 8.06 hours. This finding provided the first conclusive evidence that natural short sleep is, at least in some cases, genetic. But this mutation is rare, so while it helped explain some natural short sleepers, it couldn't account for all of them.

"Sleep is complicated," said UCSF's Louis Ptáček, MD, the John C. Coleman Distinguished Professor in Neurodegenerative Diseases and co-senior author of the new study. "We didn't think there was just one gene or one region of the brain telling our bodies to sleep or wake." Ptáček and Fu reasoned that there had to be other, as yet undiscovered, causes of short sleep.

As the new study describes, a breakthrough came when the researchers identified a family that included three successive generations of natural short sleepers, none of whom harbored the DEC2 mutation. The researchers used gene sequencing and a technique known as linkage analysis, which helps scientists pinpoint the exact chromosomal location of mutations associated with a particular trait, to comb through the family's genome. Their efforts uncovered a single-letter mutation in a gene known as ADRB1 that, like the mutation in DEC2, was associated with natural short sleep.

Eager to understand how the newly discovered mutation might lead to short sleep, the researchers performed a series of experiments in lab-grown cells and in mice that had been genetically engineered to harbor an identical mutation in the mouse version of ADRB1.

The cell-based experiments revealed that the mutant form of the beta-1 adrenergic receptor - the protein encoded by the ADRB1 gene, which plays a role in a variety of essential biological processes - degrades more rapidly than the non-mutant version, suggesting that it might also function differently.

This hunch was confirmed in mouse experiments. The researchers discovered that the ADRB1 gene was highly expressed in the dorsal pons, a region of the brainstem involved in regulating sleep. Using a technique known as optogenetics, in which cells are modified so they can be activated by light, the researchers focused light on neurons in the pons to stimulate those in which ADRB1 was expressed. Triggering these neurons immediately roused sleeping mice - specifically, those that were experiencing non-REM sleep, the sleep phase during which these neurons are not normally active - demonstrating that these neurons promote wakefulness.

Additional experiments showed that wakefulness-promoting neurons in the pons with the mutated version of ADRB1 were more easily activated. Furthermore, the ratio of wakefulness-promoting to sleep-promoting neurons skewed heavily towards the former in mice with the ADRB1 mutation. These experiments suggest that the mutant form of ADRB1 promotes natural short sleep because it helps build brains that are easier to rouse and that stay awake longer.

Though they sleep less, natural short sleepers don't suffer any of the adverse health effects associated with sleep deprivation. "Today, most people are chronically sleep deprived. If you need eight to nine hours, but only sleep seven, you're sleep deprived," Fu said. "This has well-known, long-term health consequences. You're more likely to suffer from cardiovascular disease, cancer, dementia, metabolic problems and a weakened immune system."

But natural short sleepers actually seem to benefit from this quirk of their biology. Fu says researchers have found that short sleepers tend to be more optimistic, more energetic and better multitaskers. They also have a higher pain threshold, don't suffer from jet lag and some researchers believe they may even live longer. Though the exact reasons for these benefits remain unknown, Fu and Ptáček think their work represents an important step toward understanding the connection between good sleep and overall health.

"Natural short sleepers experience better sleep quality and sleep efficiency," Fu said. "By studying them, we hope to learn what makes for a good night's sleep, so that all of us can be better sleepers leading happier, healthier lives."

Authors: Additional authors of the study include Guangsen Shi, Lijuan Xing, David Wu, Bula J. Bhattacharyya, Thomas McMahon, S.Y. Christin Chong and Andrew Krystal of UCSF; Christopher R. Jones of the University of Utah; Jason A. Chen, Giovanni Coppola and Daniel Geschwind of UCLA.

Funding: This study was supported by the NINDS Informatics Center for Neurogenetics and Neurogenomics (grant P30 NS062691), the NIH (grants NS099333, NS072360, NS104782 and P30 DK063720), and the William Bowes Neurogenetics Fund.

Disclosures: The authors declare no competing interests.
The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. Related Stories: Scientists Discover How Gene Mutation Reduces the Need for Sleep The Science of Sleep: A Q&A With Neurology Professor Ying-Hui Fu

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After 10-Year Search, Scientists Find Second 'Short Sleep' Gene

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After a decade of searching, the UC San Francisco scientists who identified the only human gene known to promote "natural short sleep" - lifelong, nightly sleep that lasts just four to six hours yet leaves individuals feeling fully rested - have discovered a second.

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Does an increase in sleep lead to an increase in cognitive performance?

I investigated the question of it a greater amount of sleep results in greater cognitive performance. My investigation clearly resulted in my question being correct. However, there were some people known as short sleepers who this didn't apply to.

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My Grades
Describes how the reviewing of my high school transcripts connects lower grades to being sleep deprived. I compare the grades of my first period classes to see if they result in my worst grade for that semester. Results that I received my worst grade in my first period for four of the seven semester. This demonstrates that there can be a correlation in lack of academic performance as "This equals about 57% of the time which is surprising since I thought I always received my worst grade in my first period"

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The Brain: The Story of You
Describes how the brain evolves from infancy to adulthood. Also goes over how our brain works and allows us to do certain thing such as experience our five senses. In the book it goes over a case where someone had a tumor that was pressing against a certain part of the brain resulting in altered behavior. This supports my claim in the way that it supports the idea that the brain can be altered, such as the effects via a lack of sleep. "This small amount of pressure on the amygdala led to a cascade of consequences in Whitman’s brain, resulting in him taking actions that would otherwise be completely out of character."

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Causes of Sleep Deprivation and Its Effect on Performance of Students and Their Mental Health
Describes how sleep deprivation affects a students life. Explores what some of the causes are that can lead to sleep deprivation in a students life. States that the amount of hours slept correlates to a students grades; a greater amount of sleep results in higher grades. But not only leads to worse grades but psychological distresses like anxiety and depression. This supports the claim that less sleep affects the brain to have lower cognitive abilities. Leading to support the idea that a greater amount of sleep creates better brain health and results in greater cognitive abilities. A study was done where "students who got more sleep(over 9 hours) had higher GPA than the ones getting less sleep(under 6 hours). They were 3.24 versus 2.74 respectively."

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Causes of sleep deprivation and its effect on performance of students

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Effects of Sleep Deprivation on the Tryptophan Metabolism
Describes how sleep disorders effects the brains biochemical and behavioral functions. Explores the effects of the amino acid Tryptophan on the brain. Demonstrates that Tryptophan is catabolised through the Kynurenine pathway, but when the levels of Kynurenine are too high it leads to the formation of KYNA. This supports my claim that sleep does have an affect on the brains health and this shows how if affects it biologically. "Increased KYNA levels in the brain are associated with increased cognitive deficits, whereas decreased KYNA levels, have been reported to improve learning and memory because they impair both glutamatergic and cholinergic transmission".

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Effects of Sleep Deprivation on the Tryptophan Metabolism