Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer’s Disease and the Blood-Brain Barrier

Abstract

Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline in elderly people and development of Alzheimer’s disease (AD). Blood–brain barrier (BBB) leakage is a key pathophysiological mechanism of amyloidal CSVD. Sleep plays a crucial role in keeping health of the central nervous system and in resistance to CSVD. The deficit of sleep contributes to accumulation of metabolites and toxins such as beta-amyloid in the brain and can lead to BBB disruption. Currently, sleep is considered as an important informative platform for diagnosis and therapy of AD. However, there are no effective methods for extracting of diagnostic information from sleep characteristics. In this review, we show strong evidence that slow wave activity (SWA) (0–0.5 Hz) during deep sleep reflects glymphatic pathology, the BBB leakage and memory deficit in AD. We also discuss that diagnostic and therapeutic targeting of SWA in AD might lead to be a novel era in effective therapy of AD. Moreover, we demonstrate that SWA can be pioneering non-invasive and bed–side technology for express diagnosis of the BBB permeability. Finally, we review the novel data about the methods of detection and enhancement of SWA that can be biomarker and a promising therapy of amyloidal CSVD and CSVD associated with the BBB disorders.

WITHDRAWN: Sleep Treatment Improves Neuropsychological Symptoms and Reduces Blood Aβ42/pTau Protein in Alzheimer's Disease Patients: a Longitudinal Study

“…In recent years, sleep disorders are linked to Alzheimer's disease progression in addition to the typical symptoms of progressive loss of memory, speech and cognition 12,13 . A high prevalence (25-66%) of Alzheimer's disease patients was reported to exhibit various types of sleep disorders, including excessive daytime sleepiness (EDS), sundowning, nocturnal wandering, sunset syndrome, sleep breathing disorder (SBD) and insomnia 14 .…”

A Novel Method to Stimulate Lymphatic Clearance of Beta-Amyloid from Mouse Brain Using Non-invasive Music-Induced Opening of the Blood-Brain Barrier with EEG Markers

“…Further studies of this hypothesis will shed light on the mechanisms by which Aβ is cleared from the brain. In our recent review, we discussed that the EEG dynamics can be a potential biomarker of BBB integrity [25]. Here we propose the EDFA analysis of EEG data and show that OBBB can be identified based on the EEG data using long-range power-law correlations.…”

“…Currently, it has been discussed that the electroencephalographic (EEG) dynamics can be a potential biomarker of BBB integrity [25]. In our preliminary studies, we were demonstrated the successful application of nonlinear analysis of EEG patterns in the evaluation of OBBB [26][27][28][29][30][31].…”

Photostimulation of lymphatic clearance of red blood cells from the mouse brain after intraventricular hemorrhage

“…The PS-lymphatic therapy can be important also for silent SAH and subdural hemorrhages, which are located superficially and are identified in 46-50% of mature babies [52]. Our data are limited by the study of one protocol of PS influences on the lymphatic evacuation of RBCs, while it has actively discussed that sleep can be a natural factor of activation of the lymphatic functions in the brain [53]. We assume that PS application during deep sleep can significantly enhances therapeutic effects of PS on brain bleedings and causes more pronounced influences on regenerative lymphatic mechanisms.…”