Nisha Pandey

Alzheimer's Sleep Loss May Be Reversible; Study Sparks Hope For New Treatments

Sleep disturbances are among the most debilitating symptoms of Alzheimer’s disease. It often appears years before significant memory decline and other symptoms. 

A new study from researchers at the University of Kentucky suggests that this sleep loss may not be permanent. 

Instead, it could be driven by an immune response in the brain that may be reversible, sparking hope for new treatments. 

Published in the journal <em>Alzheimer’s &amp; Dementia</em>, the study found that brain immune cells called microglia, rather than amyloid plaques themselves, are the primary cause of sleep disruption in Alzheimer’s disease. 

In mouse-based trials, researchers were able to restore more than two hours of sleep per day by temporarily removing these immune cells, without reducing amyloid plaques. 

<h2>Can Sleep Be Restored In Alzheimer’s Patients? </h2>

For years, scientists believed that sleep problems in <a href="https://www.healthandme.com/health-wellness/prone-to-developing-cold-sores-you-may-be-risk-for-this-cognitive-disease-article-151694503" data-type="tilCustomLink">Alzheimer’s</a> were caused by the accumulation of amyloid plaques or the gradual death of brain cells. However, this study points in a different direction. 

Researchers discovered that when amyloid plaques begin forming in the brain, they activate microglia, the brain’s resident immune cells. 

Instead of protecting the brain, these cells cause inflammation that keeps brain circuits active, preventing sleep. 

Using a drug called pexidartinib (PLX3397), the researchers temporarily depleted around 87% of microglia in Alzheimer’s mouse models. 

This restored over two hours of daily sleep, particularly non-rapid eye movement (NREM) sleep, which is essential for tissue repair, memory strengthening, and clearing waste products from the brain. 

Notably, the improvement occurred without changing amyloid plaque levels, suggesting that <a href="https://www.healthandme.com/health-wellness/not-just-the-heart-obesity-in-midlife-could-be-just-as-harmful-to-the-brain-study-article-155192003" data-type="tilCustomLink">inflammation</a> is manageable.

Also read: <a href="https://www.healthandme.com/health-news/captain-sully-sullenberger-miracle-on-the-hudson-pilot-reveals-early-stage-alzheimers-diagnosis-article-155101166" data-type="tilCustomLink">Captain ‘Sully’ Sullenberger, ‘Miracle On The Hudson’ Pilot, Reveals Early-Stage Alzheimer’s Diagnosis</a>

Lead researcher Dr. Shannon L. Macauley, associate professor of physiology at the University of Kentucky College of Medicine, said, “Basically, we showed that it is not the plaques themselves, or solely dysfunctional neurons, that cause sleep loss but actually microglia. 

Microglia are immune cells that, when they respond to plaques, kick off this elaborate cascade of inflammation, as if the microglia are partying all night, and keeping the brain awake.” 

She also highlighted why losing restorative sleep can accelerate disease progression. 

“That restorative sleep is super important for physical repair, learning and memory and washing out the toxins of the day. When Alzheimer’s patients lose this stage, they lose their brain’s primary cleaning cycle, creating a feed-forward loop that may drive further damage,” she explained. 

First author Dr. Nicholas J. Constantino said one of the biggest surprises was that <a href="https://www.healthandme.com/health-wellness/world-brain-day-climate-change-is-not-just-harming-the-planet-it-could-also-be-affecting-your-brain-article-155151944" data-type="tilCustomLink">sleep problems</a> did not worsen as amyloid plaques increased. 

“I expected that as plaque burden became more severe, sleep disruption would also worsen. The disruptions in sleep… did not worsen by 18 months, despite more than double the amount of plaque burden,” Constantino said.

Also read: <a href="https://www.healthandme.com/health-wellness/what-is-type-3-diabetes-insulin-resistance-in-the-brain-that-could-trigger-alzheimers-article-151103489" data-type="tilCustomLink">What Is Type 3 Diabetes? Insulin Resistance In The Brain That Could Trigger Alzheimer’s</a>

<h2>Why Do Alzheimer’s Patients Lose Sleep? </h2>

Before You Take Another Paracetamol, Watch This | Doctors Explain the Hidden Risk

Poor sleep and Alzheimer’s create a vicious cycle. <a href="https://www.healthandme.com/health-wellness/ncrs-long-commutes-are-stealing-sleep-affecting-reproductive-health-article-155175092" data-type="tilCustomLink">Sleep deprivation</a> reduces the brain’s ability to clear amyloid-beta and tau proteins, which can accelerate disease progression, while worsening sleep. 

Sleep disturbances affect up to half of people living with Alzheimer’s disease. The disease disrupts sleep due to various reasons: 

Overactive microglia: As shown in the new study, immune cells become chronically activated by amyloid plaques, releasing inflammatory signals that keep the brain in a heightened state of activity. 

Damage to sleep-regulating brain regions: Alzheimer’s progressively affects areas like the hypothalamus and brainstem that regulate the sleep-wake cycle. 

Loss of NREM sleep: Due to lack of deep sleep, the brain’s ability to clear metabolic waste, including amyloid plagues weakens. 

Circadian rhythm disruption: Degeneration of the brain’s internal clock leads to broken sleep and daytime drowsiness. This fuels confusion and agitation associated with the disease.

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Sleep disturbances are among the most debilitating symptoms of Alzheimer’s disease. It often appears years before significant memory decline and other symptoms. A new study from researchers at the University of Kentucky suggests that this sleep loss may not be permanent. Instead, it could be driven by an immune response in the brain that may be reversible, sparking hope for new treatments. Published in the journal Alzheimer’s & Dementia, the study found that brain immune cells called microglia, rather than amyloid plaques themselves, are the primary cause of sleep disruption in Alzheimer’s disease. In mouse-based trials, researchers were able to restore more than two hours of sleep per day by temporarily removing these immune cells, without reducing amyloid plaques. Can Sleep Be Restored In Alzheimer’s Patients? For years, scientists believed that sleep problems in Alzheimer’s were caused by the accumulation of amyloid plaques or the gradual death of brain cells. However, this study points in a different direction. Researchers discovered that when amyloid plaques begin forming in the brain, they activate microglia, the brain’s resident immune cells. Instead of protecting the brain, these cells cause inflammation that keeps brain circuits active, preventing sleep. Using a drug called pexidartinib (PLX3397), the researchers temporarily depleted around 87% of microglia in Alzheimer’s mouse models. This restored over two hours of daily sleep, particularly non-rapid eye movement (NREM) sleep, which is essential for tissue repair, memory strengthening, and clearing waste products from the brain. Notably, the improvement occurred without changing amyloid plaque levels, suggesting that inflammation is manageable.Also read: Captain ‘Sully’ Sullenberger, ‘Miracle On The Hudson’ Pilot, Reveals Early-Stage Alzheimer’s Diagnosis'Paradigm Shifting' Findings Lead researcher Dr. Shannon L. Macauley, associate professor of physiology at the University of Kentucky College of Medicine, said, “Basically, we showed that it is not the plaques themselves, or solely dysfunctional neurons, that cause sleep loss but actually microglia. Microglia are immune cells that, when they respond to plaques, kick off this elaborate cascade of inflammation, as if the microglia are partying all night, and keeping the brain awake.” She also highlighted why losing restorative sleep can accelerate disease progression. “That restorative sleep is super important for physical repair, learning and memory and washing out the toxins of the day. When Alzheimer’s patients lose this stage, they lose their brain’s primary cleaning cycle, creating a feed-forward loop that may drive further damage,” she explained. First author Dr. Nicholas J. Constantino said one of the biggest surprises was that sleep problems did not worsen as amyloid plaques increased. “I expected that as plaque burden became more severe, sleep disruption would also worsen. The disruptions in sleep… did not worsen by 18 months, despite more than double the amount of plaque burden,” Constantino said.Also read: What Is Type 3 Diabetes? Insulin Resistance In The Brain That Could Trigger Alzheimer’sWhy Do Alzheimer’s Patients Lose Sleep?          Poor sleep and Alzheimer’s create a vicious cycle. Sleep deprivation reduces the brain’s ability to clear amyloid-beta and tau proteins, which can accelerate disease progression, while worsening sleep. Sleep disturbances affect up to half of people living with Alzheimer’s disease. The disease disrupts sleep due to various reasons: Overactive microglia: As shown in the new study, immune cells become chronically activated by amyloid plaques, releasing inflammatory signals that keep the brain in a heightened state of activity. Damage to sleep-regulating brain regions: Alzheimer’s progressively affects areas like the hypothalamus and brainstem that regulate the sleep-wake cycle. Loss of NREM sleep: Due to lack of deep sleep, the brain’s ability to clear metabolic waste, including amyloid plagues weakens. Circadian rhythm disruption: Degeneration of the brain’s internal clock leads to broken sleep and daytime drowsiness. This fuels confusion and agitation associated with the disease.

alzheimer's sleep loss may be reversible; study sparks hope for new treatments

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