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Alzheimer's disease (AD), the most common form of dementia, brings great misfortune to patients and their families
.
Even more frightening is that every 3 seconds, there is a new patient in the world, and this number is still rising with the aging of the population
.
It is estimated that by 2050, the number of Alzheimer's patients worldwide will increase to more than 150 million
.
Regrettably, this field has so far failed to unravel the specific mechanisms of Alzheimer's disease pathogenesis
.
Under normal conditions, the levels of beta-amyloid (Aβ) in the cerebrospinal fluid of healthy adults fluctuate daily: more during the day and less at night (to be cleared)
.
However, with age or other reasons, the fluctuations become more irregular, leading to Aβ accumulation in the brain and neurofibrillary tangles composed of hyperphosphorylated tau protein that drives Alzheimer's disease
.
This is also the mainstream view in the field so far
.
Therefore, aging is the biggest risk factor for Alzheimer's disease
.
However, before aging, it is likely that you have planted the "seeds" of dementia
.
Past research has found that just one night of poor sleep can lead to an increase in Aβ, while a week of poor sleep can also lead to an accumulation of tau protein
.
Sleep disturbances that begin years before Alzheimer's symptoms appear are associated with an increased risk of later onset and more severe symptoms
.
Thus, Alzheimer's disease has a bidirectional relationship with circadian rhythm disturbances
.
It is well known that the circadian rhythm is an endogenous timing system (circadian clock) with a 24-hour cycle, which is affected by natural light and controls a series of biological processes in the body, including hormone secretion, metabolic cycling, and immune protection against pathogens, and also induces Our natural rhythm-filled behaviors, such as eating and sleep-wake cycles
.
Simply put, what to do at what time, the circadian rhythm has been arranged, not subject to human will
.
Therefore, synchronizing with the circadian rhythm is essential for good health, and staying up late, sleep deprivation or sleep disturbance can cause the body's circadian rhythm to be disturbed, so that the daily "night shift" of the immune cells responsible for clearing the accumulated waste in the brain throughout the day works time decrease, causing Aβ to start accumulating in the brain
.
Moreover, this process may further "add up" due to lack of sleep in the future
.
Therefore, chronic sleep deprivation means being at risk for more than one disease
.
However, until now, scientists have been unable to directly link circadian rhythms to the activity of immune cells responsible for clearing amyloid
.
In a new study published in PLOS Genetics on February 10, 2022, a research team led by Rensselaer Polytechnic Institute has found a molecular "timer" that controls immune cells by studying their rhythmic activity.
, thereby uncovering a potential mechanism linking circadian rhythm disturbances to β-amyloid (Aβ) accumulation
.
In earlier research, the team found that macrophage RNA and protein levels fluctuate according to daily circadian rhythms
.
Macrophages are the "scavengers" of immune cells, responsible for engulfing waste, defective proteins and dead cells, thereby preventing toxic damage
.
Macrophages migrate into the brain in advanced Alzheimer's disease
.
In the new study, using bone marrow-derived macrophages (BMDM) as a surrogate, the researchers found that fluctuations in some enzymes produce two proteins, heparan sulfate and sulfate, on the surface of macrophages.
Chondroitin sulfate
.
Reducing the levels of these two proteins helps macrophages clear the Aβ42 protein from the brain
.
But when the circadian clock was disrupted, the rhythm of macrophages was rapidly disrupted and, as levels of heparan sulfate increased, slowed the clearance of Aβ42
.
Subsequently, in experiments testing the link between the circadian cycle and these cell surface proteins, the researchers found that healthy macrophage uptake of Aβ42 protein could fluctuate with daily circadian rhythms, but not in immune cells without core clock regulation The same pattern was not observed
.
In addition, in healthy macrophages with normal circadian rhythms, both cells showed minimal levels of the protein, allowing immune cells to do a better job of clearing the harmful proteins that cause Alzheimer's
.
"Clearly, it's all orchestrated by circadian rhythms," said Jennifer Hurley, an associate professor of biological sciences and a circadian rhythm expert and corresponding author of the study
.
When there are large amounts of these cell surface proteins, macrophages cannot take up Aβ42 in sufficient quantities
.
Determine why this is the case, but there must be some connection
.
" She concluded: "Theoretically, if we can increase this rhythm, maybe we can enhance the ability to clear the Aβ42 protein, thereby preventing damage to the brain
.
"Link to the paper: https://doi.
org/10.
1371/journal.
pgen.
1009994 Related reading: Heart: My life depends on the "day"! Scientists discover the causal link between staying up late and causing heart disease Because your immune system doesn't stay up with you.
.
.
staying up late + high-fat diet, the impact on health or "lifetime".
.
.
.
Even more frightening is that every 3 seconds, there is a new patient in the world, and this number is still rising with the aging of the population
.
It is estimated that by 2050, the number of Alzheimer's patients worldwide will increase to more than 150 million
.
Regrettably, this field has so far failed to unravel the specific mechanisms of Alzheimer's disease pathogenesis
.
Under normal conditions, the levels of beta-amyloid (Aβ) in the cerebrospinal fluid of healthy adults fluctuate daily: more during the day and less at night (to be cleared)
.
However, with age or other reasons, the fluctuations become more irregular, leading to Aβ accumulation in the brain and neurofibrillary tangles composed of hyperphosphorylated tau protein that drives Alzheimer's disease
.
This is also the mainstream view in the field so far
.
Therefore, aging is the biggest risk factor for Alzheimer's disease
.
However, before aging, it is likely that you have planted the "seeds" of dementia
.
Past research has found that just one night of poor sleep can lead to an increase in Aβ, while a week of poor sleep can also lead to an accumulation of tau protein
.
Sleep disturbances that begin years before Alzheimer's symptoms appear are associated with an increased risk of later onset and more severe symptoms
.
Thus, Alzheimer's disease has a bidirectional relationship with circadian rhythm disturbances
.
It is well known that the circadian rhythm is an endogenous timing system (circadian clock) with a 24-hour cycle, which is affected by natural light and controls a series of biological processes in the body, including hormone secretion, metabolic cycling, and immune protection against pathogens, and also induces Our natural rhythm-filled behaviors, such as eating and sleep-wake cycles
.
Simply put, what to do at what time, the circadian rhythm has been arranged, not subject to human will
.
Therefore, synchronizing with the circadian rhythm is essential for good health, and staying up late, sleep deprivation or sleep disturbance can cause the body's circadian rhythm to be disturbed, so that the daily "night shift" of the immune cells responsible for clearing the accumulated waste in the brain throughout the day works time decrease, causing Aβ to start accumulating in the brain
.
Moreover, this process may further "add up" due to lack of sleep in the future
.
Therefore, chronic sleep deprivation means being at risk for more than one disease
.
However, until now, scientists have been unable to directly link circadian rhythms to the activity of immune cells responsible for clearing amyloid
.
In a new study published in PLOS Genetics on February 10, 2022, a research team led by Rensselaer Polytechnic Institute has found a molecular "timer" that controls immune cells by studying their rhythmic activity.
, thereby uncovering a potential mechanism linking circadian rhythm disturbances to β-amyloid (Aβ) accumulation
.
In earlier research, the team found that macrophage RNA and protein levels fluctuate according to daily circadian rhythms
.
Macrophages are the "scavengers" of immune cells, responsible for engulfing waste, defective proteins and dead cells, thereby preventing toxic damage
.
Macrophages migrate into the brain in advanced Alzheimer's disease
.
In the new study, using bone marrow-derived macrophages (BMDM) as a surrogate, the researchers found that fluctuations in some enzymes produce two proteins, heparan sulfate and sulfate, on the surface of macrophages.
Chondroitin sulfate
.
Reducing the levels of these two proteins helps macrophages clear the Aβ42 protein from the brain
.
But when the circadian clock was disrupted, the rhythm of macrophages was rapidly disrupted and, as levels of heparan sulfate increased, slowed the clearance of Aβ42
.
Subsequently, in experiments testing the link between the circadian cycle and these cell surface proteins, the researchers found that healthy macrophage uptake of Aβ42 protein could fluctuate with daily circadian rhythms, but not in immune cells without core clock regulation The same pattern was not observed
.
In addition, in healthy macrophages with normal circadian rhythms, both cells showed minimal levels of the protein, allowing immune cells to do a better job of clearing the harmful proteins that cause Alzheimer's
.
"Clearly, it's all orchestrated by circadian rhythms," said Jennifer Hurley, an associate professor of biological sciences and a circadian rhythm expert and corresponding author of the study
.
When there are large amounts of these cell surface proteins, macrophages cannot take up Aβ42 in sufficient quantities
.
Determine why this is the case, but there must be some connection
.
" She concluded: "Theoretically, if we can increase this rhythm, maybe we can enhance the ability to clear the Aβ42 protein, thereby preventing damage to the brain
.
"Link to the paper: https://doi.
org/10.
1371/journal.
pgen.
1009994 Related reading: Heart: My life depends on the "day"! Scientists discover the causal link between staying up late and causing heart disease Because your immune system doesn't stay up with you.
.
.
staying up late + high-fat diet, the impact on health or "lifetime".
.
.
