amyloid-beta-peptides and Sleep-Wake-Disorders

As a normal physiological process, sleep has recently been shown to facilitate clearance of macromolecular metabolic wastes from the brain via the glymphatic system. The aim of the present study was to investigate pathophysiological roles of astroglial aquaporin 4 (AQP4), a functional regulator of glymphatic clearance, in a mouse model of chronic sleep disruption (SD).. Adult AQP4 null mice and wild-type (WT) mice were given 7 days of SD using the improved rotating rod method, and then received behavioral, neuropathological, and neurochemical analyses.. Aquaporin 4 deletion resulted in an impairment of glymphatic transport and accumulation of β-amyloid and Tau proteins in the brain following SD. AQP4 null SD mice exhibited severe activation of microglia, neuroinflammation, and synaptic protein loss in the hippocampus, as well as decreased working memory, compared with WT-SD mice.. These results demonstrate that AQP4-mediated glymphatic clearance ameliorates brain impairments caused by abnormal accumulation of metabolic wastes following chronic SD, thus serving as a potential target for sleep-related disorders.

Topics: Amyloid beta-Peptides; Animals; Aquaporin 4; Brain; Corticosterone; Gene Deletion; Glymphatic System; Hippocampus; Male; Memory, Short-Term; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; NLR Family, Pyrin Domain-Containing 3 Protein; Peptide Fragments; Recognition, Psychology; Sleep Wake Disorders; Spatial Memory; tau Proteins

Sleep disturbances are associated with future risk of Alzheimer disease. Disrupted sleep increases soluble amyloid β, suggesting a mechanism for sleep disturbances to increase Alzheimer disease risk. We tested this response in humans using indwelling lumbar catheters to serially sample cerebrospinal fluid while participants were sleep-deprived, treated with sodium oxybate, or allowed to sleep normally. All participants were infused with

Topics: Adult; Alzheimer Disease; Amyloid beta-Peptides; Anesthetics; Circadian Rhythm; Female; Humans; Kinetics; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Peptide Fragments; Pilot Projects; Sleep; Sleep Wake Disorders; Sodium Oxybate

To determine the relationship between sleep quality and CSF markers of Alzheimer disease (AD) pathology in late midlife.. We investigated the relationship between sleep quality and CSF AD biomarkers in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention. A total of 101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal. Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 [Aβ42]), tau pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation (monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein 1 [YKL-40]), and synaptic dysfunction/degeneration (neurogranin). To adjust for individual differences in total amyloid production, Aβ42 was expressed relative to Aβ40. To assess cumulative pathology, CSF biomarkers were expressed in ratio to Aβ42. Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.. Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42. There were no significant associations between sleep and NFL or neurogranin.. Self-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.

Topics: Amyloid beta-Peptides; Biomarkers; Chemokine CCL2; Chitinase-3-Like Protein 1; Female; Humans; Longitudinal Studies; Male; Mental Status Schedule; Middle Aged; Neurofilament Proteins; Nuclear Proteins; Peptide Fragments; Phosphorylation; RNA-Binding Proteins; Self Report; Sleep; Sleep Wake Disorders; tau Proteins

To study the association between self-reported sleep disturbances and dementia risk.. Self-reported sleep disturbances and established risk factors for dementia were measured in men at ages 50 (n = 1574) and 70 (n = 1029) years. Dementia incidence was determined by reviewing their patient history between ages 50 and 90 years. In addition, plasma levels of β-amyloid (Aβ) peptides 1-40 and 1-42 were measured at ages 70, 77, and 82 years.. Cox regression demonstrated that men with self-reported sleep disturbances had a higher risk of developing dementia (+33%) and Alzheimer's disease (AD, +51%) than men without self-reported sleep disturbances (both P < .05). Binary logistic regression showed the increased risk for both dementia (+114%) and AD (+192%) were highest when sleep disturbance was reported at age 70 years (both P < .001). No group differences were found in Aβ levels.. Improving sleep quality may help reduce the neurodegenerative risk in older men.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Humans; Logistic Models; Longitudinal Studies; Male; Middle Aged; Peptide Fragments; Risk; Self Report; Sleep Wake Disorders; Sweden