Influence of sleep disruption on protein accumulation in neurodegenerative diseases

Abstract

Abnormal accumulation of disease proteins in the central nervous system is a neuropathological feature in neurodegenerative disorders. Recently, a growing body of evidence has supported a role of disruption of the sleep-wake cycle in disease development, pathological changes and abnormal protein accumulation in neurodegenerative diseases, especially in Alzheimer’s disease and Parkinson’s disease. Sleep deprivation promotes abnormal accumulation of disease proteins. Interestingly, amyloid-β (Aβ) has daily oscillations in human cerebral spinal fluid (CSF) and is cleared more in sleep. Both circadian genes and circadian hormones are associated with disease protein deposition. Recently, the glymphatic pathway and meningeal lymphatics have been shown to play a critical role in Aβ clearance, which is mediated by the aquaporin (AQP-4) water channel on astrocytes. The rate of the clearance of Aβ by the glymphatic pathway is different during the sleep/wake cycle. Most importantly, circadian rhythms facilitate glymphatic clearance of solutes and Aβ in the CSF and interstitial fluid in an AQP-4-dependent manner, which further provides evidence for the involvement of circadian rhythms in disease protein clearance.

The electrophysiological and neuropathological profiles of cerebellum in APPswe/PS1ΔE9 mice: A hypothesis on the role of cerebellum in Alzheimer's disease

“…23 Growing evidence has suggested that there is a bidirectional relationship between sleep disturbance and AD. 24 Although cerebellum is often considered as a motor coordinator, more recent studies indicate that it also plays an important role in the regulation of rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep, and wakefulness. 25 Cerebellar disorders have been shown to disrupt the structure of the sleep-wake cycles.…”

APPswe/PS1ΔE9 mice exhibit low oxygen saturation and alterations of erythrocytes preceding the neuropathology and cognitive deficiency during Alzheimer's disease

“…Alzheimer's disease (AD) is the most common neurodegenerative disease. AD develops slowly in the brain, brain blood vessels, and peripheral tissues and is characterized by age‐associated progressive deterioration of cognitive abilities 1,2 . More than 90% of AD patients appear to be sporadic and generally with a late age of onset, while familial AD cases usually show symptoms before the age of 65 or even earlier, accounting for 2%–5% of AD cases 3 .…”

Association of Glial Activation and α-Synuclein Pathology in Parkinson’s Disease

“…Although 5%-10% of PD cases are familial, the majority of cases are sporadic [3,6]. The hallmarks of pathological changes in PD are the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the deposition of α-synuclein (α-syn) in Lewy bodies (LBs) and neurites (LNs) that are widely distributed in the brains of PD cases [6][7][8][9]. The LBs are composed of phosphorylated α-syn (S129), ubiquitinated proteins, and other damaged organelle components [10][11][12].…”