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Review
. 2022 Jun 9:16:875138.
doi: 10.3389/fncel.2022.875138. eCollection 2022.

Possible Neuropathology of Sleep Disturbance Linking to Alzheimer's Disease: Astrocytic and Microglial Roles

Shu-Yun Xiao  1 , Yi-Jie Liu  2   3 , Wang Lu  4 , Zhong-Wei Sha  1 , Che Xu  5 , Zhi-Hua Yu  6 , Shin-Da Lee  1   7   8
Affiliations
Review

Possible Neuropathology of Sleep Disturbance Linking to Alzheimer's Disease: Astrocytic and Microglial Roles

Shu-Yun Xiao et al. Front Cell Neurosci. .

Abstract

Sleep disturbances not only deteriorate Alzheimer's disease (AD) progress by affecting cognitive states but also accelerate the neuropathological changes of AD. Astrocytes and microglia are the principal players in the regulation of both sleep and AD. We proposed that possible astrocyte-mediated and microglia-mediated neuropathological changes of sleep disturbances linked to AD, such as astrocytic adenosinergic A1, A2, and A3 regulation; astrocytic dopamine and serotonin; astrocyte-mediated proinflammatory status (TNFα); sleep disturbance-attenuated microglial CX3CR1 and P2Y12; microglial Iba-1 and astrocytic glial fibrillary acidic protein (GFAP); and microglia-mediated proinflammatory status (IL-1b, IL-6, IL-10, and TNFα). Furthermore, astrocytic and microglial amyloid beta (Aβ) and tau in AD were reviewed, such as astrocytic Aβ interaction in AD; astrocyte-mediated proinflammation in AD; astrocytic interaction with Aβ in the central nervous system (CNS); astrocytic apolipoprotein E (ApoE)-induced Aβ clearance in AD, as well as microglial Aβ clearance and aggregation in AD; proinflammation-induced microglial Aβ aggregation in AD; microglial-accumulated tau in AD; and microglial ApoE and TREM2 in AD. We reviewed astrocytic and microglial roles in AD and sleep, such as astrocyte/microglial-mediated proinflammation in AD and sleep; astrocytic ApoE in sleep and AD; and accumulated Aβ-triggered synaptic abnormalities in sleep disturbance. This review will provide a possible astrocytic and microglial mechanism of sleep disturbance linked to AD.

Keywords: Alzheimer’s disease; amyloid beta; astrocyte; microglia; sleep disturbance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Astrocyte and microglial roles in sleep disturbance linked Alzheimer’s disease. Sleep and CNS immune influence each other. Microglial responses in the sleep/wake are essential for Aβ clearance and inflammatory activation. Aβ accumulation induces abnormal mitochondrial function in microglia which further activates the release of inflammatory cytokines, while Aβ clearance by microglia phagocytosis relies on the stimulation of Aβ itself. TREM2 in the microglia membrane combines with Aβ and then enhances its ability on Aβ phagocytosis. The downregulated TXNIP induces ROS inhibition and further causes DNA damage during sleep disorders. On the contrary, lower TXNIP under sleep disturbances could increase NLRP3 inflammasome activation and IL-1β-initiated inflammatory response. Apart from the role in Aβ clearance and Aβ involved inflammation, microglia directly participate in synapse removal or “synaptic stripping,” and this is regulated by normal sleep/wake rhythm.
FIGURE 2
FIGURE 2
Astrocyte and microglial roles in sleep disturbance linked Alzheimer’s disease. Sleep disturbances accelerate the neuropathological changes of AD. During normal sleep/wake rhythm, astrocytic adenosinergic A1, A2, and A3 inhibit neural overactivation, while sleep disturbance attenuates microglial CX3CR1 and P2Y12 further inhibiting the phagocytic capacity of microglia. Abnormal sleep rhythms also promote microglial Iba-1 and astrocytic glial fibrillary acidic protein (GFAP) and increase microglia-mediated proinflammatory releases, such as IL-1b, IL-6, IL-10, and TNFα. Activated inflammatory status further induces microglial Aβ aggregation and microglial-accumulated tau in AD.
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