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The Impact of Sleep Deprivation on Alzheimer's Disease

Mechanisms Linking Sleep Deficiency and Alzheimer's Disease

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Sleep deficiency, characterized by insufficient sleep duration or poor sleep quality, is a prevalent health concern in modern society.[1] It has been linked to an increased risk of Alzheimer's disease (AD).[1] The mechanisms by which sleep deficiency affects AD are not fully understood, but research suggests several pathways are involved.

Amyloid-Beta (Aβ) Deposition

Several mechanisms connect sleep deficiency to the development and progression of AD. These include:

Tau Protein Hyperphosphorylation

Preclinical studies have shown that Aβ, a metabolic waste product, exhibits diurnal fluctuations in the brain, with secretion increasing during wakefulness and decreasing during sleep.[18] Sleep deprivation can lead to increased Aβ levels and potentially promote plaque deposition.[19] Studies have shown that Aβ levels in the cerebrospinal fluid increase significantly in healthy individuals during sleep deprivation, and this change is reversed during good sleep.[22]

Oxidative Stress

Tau protein, which regulates microtubule stability, becomes hyperphosphorylated in AD, leading to the formation of neurofibrillary tangles (NFTs).[26] Insufficient sleep has been linked to increased levels of tau protein in the brain and cerebrospinal fluid.[29] Animal models have shown that changes in sleep-wake cycles can increase hyperphosphorylated tau protein levels.[30]

Neuroinflammation

Sleep deprivation is associated with increased production of free radicals, leading to oxidative stress.[34] This can damage brain cells and contribute to AD pathogenesis.[35]

Sleep deficiency can disrupt the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased levels of glucocorticoids, such as cortisol.[49] Elevated cortisol levels may promote neuronal loss and accelerate cognitive decline.[50]

Glucocorticoid Levels

Long-term sleep deficiency can lead to chronic systemic low-grade inflammation, which is associated with various inflammatory diseases.[42] Excessive microglial activation releases inflammatory factors and promotes neuroinflammation.[41]

Brain-Derived Neurotrophic Factor (BDNF)

Sleep deficiency reduces synaptic plasticity, which impairs learning and memory and increases the risk of cognitive impairment.[58]

Synaptic Plasticity

Conclusion

BDNF, a neurotrophic protein, is down-regulated in both AD and sleep deficiency.[62] This can impair neuronal growth and survival, contributing to cognitive decline.[63]

The evidence suggests a strong link between sleep deficiency and AD. Sleep deprivation increases amyloid-beta build-up. Improving sleep quality may be an effective strategy for preventing or slowing the progression of AD.[15]

Authoritative Sources

  1. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  2. Kang J-E, et al. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. [Science]↩
  3. Ju Y-ES, et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. [Brain]↩
  4. Ooms S, et al. Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men: a randomized clinical trial. [JAMA Neurol.]↩
  5. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  6. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  7. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  8. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  9. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  10. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  11. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  12. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  13. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  14. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  15. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  16. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩
  17. Cordone S, Annarumma L, Rossini PM and De Gennaro L (2019) Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments. [Front. Pharmacol.]↩

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