Cerebrospinal Fluid Amyloid-β Levels are Increased in Patients with Insomnia

Abstract

Previous studies demonstrate that patients with sleep disorders are at risk of developing Alzheimer's disease (AD), with the mechanism unknown. It is suggested that acute sleep deprivation induces an increase of amyloid-β (Aβ), the major pathological agent in AD, in the cerebrospinal fluid (CSF). In the present study, we recruited 23 patients with chronic insomnia aged between 46 to 67 years and 23 healthy controls aged between 43 to 67 years. We investigated the CSF levels of Aβ and tau, another pathological hallmark in the AD pathogenesis. We found that CSF Aβ42 levels were significantly increased in insomnia patients. However, no significant difference was found in Aβ40, total tau (t-Tau), and phosphorylated tau (p-Tau) between the two groups. Furthermore, we found that CSF Aβ40 and Aβ42 levels are significantly correlated with the sleep quality, as reflected by the Pittsburgh Sleep Quality Index (PSQI) scores. But no significant correlation was found in CSF t-Tau and p-Tau levels with PSQI. Our results indicate that chronic sleep disorders may induce the disruption of Aβ metabolism in the brain, thus increase the risk for developing AD.

The effect of insomnia on development of Alzheimer’s disease

“…Aβ is considered as the major pathological agent of AD. It is demonstrated that insomnia can lead to an increase in the levels of Aβ of CSF and this Aβ can cause synaptic dysfunction and neurotransmission impair, essential mechanisms to the pathogenesis of AD [51,56]. Also, sleep impairment can lead to:…”

“…Aβ is considered as the major pathological agent of AD. It is demonstrated that insomnia can lead to an increase in the levels of Aβ of CSF and this Aβ can cause synaptic dysfunction and neurotransmission impair, essential mechanisms to the pathogenesis of AD [ 51 , 56 ]. Also, sleep impairment can lead to: Induction of the extracellular release of tau [ 129 , 159 ] which this increase can result in neurodegeneration and neuron loss and can explain the association of insomnia to AD pathogenesis [ 53 , 95 , 160 , 161 ].…”

“…During the 3-year follow up of 51, 743 primary insomnia patients (older than 20 years of age), after adjusting for sex, the region of residence, and selected comorbidities, a primary insomnia diagnosis was independently associated with a 2.14-fold (p value < 0.05) higher risk of subsequent development of dementia [96]. Chen et al suggested the correlation between Aβ levels of CSF with the duration of insomnia in 23 patients with chronic insomnia aged between 46 and 67 and showed long-term poor sleep quality has accumulative effects on brain Aβ42 levels [51]. It has been suggested that wakefulness increases neuronal activity, and hence the production and secretion of Aβ [97].…”

The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade

“…Poor sleep quality, which is associated with dementia, might negatively affect the activity of the glymphatic system [ 340 ]. CSF levels of Aβ have been found to be increased significantly in insomnia patients [ 361 ]. Thus, the role of the glymphatic system in AD with regards to Aβ may be that its decreased activity leads to impaired AβO clearance, which may lead to further aggregation resulting in larger AβOs or insoluble amyloid plaques, both of which the glymphatic system cannot clear.…”

Depression and Sleep

“…Specific disruption of SWA in healthy adults without sleep disorders correlated with an increase in Aβ [91]. In patients with insomnia CSF Aβ levels were significantly higher than in healthy controls [92].…”