Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract INTRODUCTION Sleep disturbances are associated with Alzheimer's disease (AD) and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, AD/ADRD biomarkers remains unclear. METHODS We enrolled 128 adults (64 disease, 41 mild cognitive impairment [MCI], 23 normal cognition [NC]), mean age 70.8 ± 9.6 years, 56.9% female, from a tertiary hospital in China. Participants underwent overnight polysomnography (PSG), amyloid β (Aβ) positron emission tomography (PET), plasma biomarker analysis: phosphorylated tau at threonine 181 (p‐tau181), neurofilament light (NfL), brain‐derived neurotrophic factor (BDNF). RESULTS After adjusting for demographics, apolipoprotein E ( APOE ) ε4 status, cognition, comorbidities, highest tertile of REM latency was higher Aβ burden = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p 0.002), elevated p‐tau181 0.19, CI: 0.02 reduced BDNF levels ‐0.47, –0.68 –0.13, 0.013), compared lowest tertile. DISCUSSION Prolonged may serve as novel marker or risk pathogenesis. Highlights Rapid (REML) be potential (AD/ADRD) REML beta burden, tau‐181 lower (BDNF) levels. Intervention trial is needed determine if targeting can modify risk. Slow‐wave not biomarkers.

Language: Английский

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Melatonin ameliorates PM2.5-induced airway inflammation and apoptosis by PERK/eIF2α/ATF4/CHOP in chronic obstructive pulmonary disease mice

Toxicology and Applied Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 117314 - 117314

Published: March 1, 2025

Language: Английский

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The Neuroprotective Role of Melatonin in Intracerebral Hemorrhage: Lessons from an Observational Study

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(5), P. 1729 - 1729

Published: March 4, 2025

Background/Objectives: Growing evidence is underscoring the neuroprotective properties of melatonin, particularly its anti-inflammatory, anti-apoptotic, and antioxidant effects. Preliminary findings suggest that it has potential to attenuate secondary brain injury following intracerebral hemorrhage (ICH). This observational study aimed investigate effect melatonin on post-ICH mortality functional outcomes. Methods: We conducted an exploratory analysis data from a single-center, non-randomized, prospective cohort involving 177 non-ventilated patients with spontaneous ICH consecutively admitted Stroke Unit at University Hospital Tübingen, Germany, between December 2015 2020. Patients received either best standard care (control group) or plus (2 mg nightly), initiated within 24 h symptom onset continued until discharge. The primary endpoint was discharge, while endpoints included 90 days favorable outcomes (modified Rankin Scale [mRS] ≤ 2) both discharge 90-day follow-up. To minimize baseline differences, propensity score matching (PSM) employed in analysis. Additionally, ordinal mRS shift performed assess patients’ status Results: In full (84 melatonin-treated vs. 93 controls), not associated any PSM (38 38 three times lower group compared control (2.6% 7.9%), although this trend did reach statistical significance (ORadj: 0.372; 95% CI: 0.036–3.843; p = 0.407). Ordinal revealed no significant association (common OR: 0.762; 0.327–1.773; 0.527). Similarly, treatment 1.519; 0.295–7.826; 0.617) outcome 0.626; 0.198–1.983; 0.426). Conclusions: Although 2 daily significantly reduce improve patients, robust preclinical safety profile warrant further exploration adequately powered, randomized-controlled clinical trials evaluate optimized dosing regimens.

Language: Английский

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Melatonin ameliorates tauopathy and ferroptosis in P301S Tau transgenic mice

Ageing and Neurodegenerative Diseases, Journal Year: 2025, Volume and Issue: 5(1)

Published: March 10, 2025

Aim: Melatonin has been found to inhibit the induced Tau hyperphosphorylation in cellular and animal models. However, underlying mechanisms are not fully understood, especially with respect ability of melatonin control Tau-related pathologies neuronal damage. Methods: 6-month-old male P301S mice were employed evaluate effects intranasally administered (10 mg/kg) on tauopathy progression ferroptosis. HT22 D1A cells also further uncover mechanism iron metabolism. Results: We verified that intranasal administration effectively improved via modulating activity several kinases, accompanied by a stifling synaptic loss, degeneration, neuroinflammation, oxidative damage transgenic mice. Moreover, restoration ferroptosis-related indicators such as accumulation hippocampal neurons, metabolism, activating Nrf2/GPX4 signaling contributed which supplementation ameliorated behavioral deficits Interestingly, we treatment may stimulate astrocytes secrete hepcidin vitro, turn helps alleviate efflux stressed conditions. Conclusion: These findings provide compelling evidence plays role improving tauopathies ferroptosis neurodegenerative disease.

Language: Английский

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From genes to drugs: targeting Alzheimer’s with circadian insights

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: March 26, 2025

Background Alzheimer’s disease (AD) is a typical neurodegenerative that presents challenges due to the lack of biomarkers identify AD. A growing body evidence highlights critical role circadian rhythms in Methods The differentially expressed clock genes (DECGs) were identified between AD and ND groups (non-demented controls). Functional enrichment analysis was executed on DECGs. Candidate diagnostic for screened by machine learning. ROC nomograms constructed evaluate candidate biomarkers. In addition, therapeutics targeting predictive through DGIdb website. Finally, mRNA–miRNA network constructed. Results Nine DECG groups. Enrichment nine indicated pathways enriched long-term potentiation entrainment. Four (GSTM3, ERC2, PRKCG, HLA-DMA) using Lasso regression, random forest, SVM, GMM. performance four evaluated curve. Furthermore, nomogram HLA-DMA are good diagnosing Single-gene GSEA main oxidative phosphorylation, neurodegeneration-multiple diseases, etc. results immune cell infiltration there significant differences 15 subsets Moreover, 23 drugs 8 PRKCG Conclusion We three associated with genes, thus providing promising therapeutic targets

Language: Английский

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Intranasal and inhaled delivery systems for targeting circadian dysfunction in neurodegenerative disorders, perspective and future outlook

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 115575 - 115575

Published: April 1, 2025

Synchronisation of the suprachiasmatic nucleus (SCN) driven endogenous clock, located within central nervous system (CNS), and exogenous time cues, is essential for maintaining circadian rhythmicity, homeostasis overall wellbeing. Disordered rhythms have been associated with various conditions, inclusive neurodegenerative disorders, such as Alzheimer's disease Parkinson's disease. Traditional pharmacological approaches to dysfunction in disorders primarily focused on oral drug delivery. Oral medications often face challenges achieving necessary systemic circulation effectively bypass blood brain barrier (BBB) reach CNS, due low or variable bioavailability. Advancements non-invasive delivery methods, orally inhaled intranasal formulations, present promising alternatives targeting CNS. Orally allows rapidly achieve high through increased bioavailability fast onset action. Additionally, therapies BBB olfactory trigeminal nerve pathways directly enter This review assesses potential treat conditions. In addition, this will explore melatonin an example enhancing therapeutic outcomes by adopting formulations improve absorption target disorder more effectively.

Language: Английский

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Circadian Disruption in Glaucoma: Causes, Consequences, and Countermeasures

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(12)

Published: Dec. 3, 2024

This review explores the intricate relationship between glaucoma and circadian rhythm disturbances. As a principal organ for photic signal reception transduction, eye plays pivotal role in coordinating body's rhythms through specialized retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs). These are critical transmitting light signals to suprachiasmatic nucleus (SCN), central clock that synchronizes physiological processes 24-hour light-dark cycle. The delves into body clock, highlighting importance of retino-hypothalamic tract conveying information from eyes SCN. It underscores melanopsin ipRGCs absorbing initiating biochemical reactions culminate synchronization SCN's firing patterns with external environment. Furthermore, discusses local within eye, such as those affecting photoreceptor sensitivity, corneal thickness, intraocular fluid outflow. emphasizes potential optical coherence tomography (OCT) studying structural losses associated disruption. Glaucomatous damage is identified cause disruption, mechanisms including oxidative stress, neuroinflammation, direct RGCs. consequences disruption complex, systemic rhythms, sleep patterns, mood, metabolism. Countermeasures, implications management, proposed focus on strategies improve health balanced melatonin timing, daylight exposure, chronotherapeutic approaches. calls further research elucidate linking develop effective interventions address this aspect disease.

Language: Английский

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Melatonin Supplementation Alleviates Impaired Spatial Memory by Influencing Aβ1-42 Metabolism via γ-Secretase in the icvAβ1-42 Rat Model with Pinealectomy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10294 - 10294

Published: Sept. 24, 2024

In the search for Alzheimer’s disease (AD) therapies, most animal models focus on familial AD, which accounts a small fraction of cases. The majority AD cases arise from stress factors, such as oxidative stress, leading to neurological changes (sporadic AD). Early in progression, dysfunction γ-secretase causes formation insoluble Aβ1-42 peptides, aggregate into senile plaques, triggering neurodegeneration, cognitive decline, and circadian rhythm disturbances. To better model sporadic we used new rat induced by intracerebroventricular administration oligomers (icvAβ1-42) combined with melatonin deficiency via pinealectomy (pin). We validated this assessing spatial memory using radial arm maze test measuring levels frontal cortex hippocampus ELISA. icvAβ1-42 + pin experienced impaired increased hippocampus, effects not seen either or alone. Chronic treatment reversed deficits reduced both structures. Our findings suggest that our is extremely valuable future research.

Language: Английский

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The role and mechanism of Aβ clearance dysfunction in the glymphatic system in Alzheimer’s disease comorbidity

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 25, 2024

Alzheimer’s disease (AD) is the leading type of dementia globally, characterized by a complex pathogenesis that involves various comorbidities. An imbalance in production and clearance amyloid β-protein (Aβ) peptides brain key pathological mechanism AD, with glymphatic system playing crucial role Aβ clearance. Comorbidities associated such as diabetes, depression, hypertension, not only affect but also impair brain’s lymphatic system. Abnormalities structure function this further weaken capabilities, presence comorbidities may exacerbate process. This paper aims to review specific mechanisms impaired via context AD comorbidities, providing new insights for prevention treatment AD. Overall, damage primarily focuses on aquaporin-4 (AQP4) perivascular spaces (PVS), suggesting maintaining health help slow progression its Additionally, given ongoing controversies regarding system, revisits discusses principles characteristics current detection methods

Language: Английский

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New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5314 - 5314

Published: Nov. 11, 2024

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 2024. We offer an overview strategies employed in drug design approaches that led notable improvements reduced hepatotoxicity. Our aim is insights into potential development new drugs. This highlights multi-target featuring heterocycles

Language: Английский

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