Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects DOI Creative Commons
Dongze Chen, Xinpei Wang, Tao Huang

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: May 17, 2022

Late-onset Alzheimer's disease (AD) is associated with sleep-related phenotypes (SRPs). The fact that whether they share a common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD SRPs by using high-definition likelihood (HDL), cross-phenotype association study (CPASSOC), transcriptome-wide (TWAS), bidirectional Mendelian randomization (MR) in summary-level data for (N = 455,258) seven (sample size ranges from 359,916 to 1,331,010). strong basis insomnia (rg 0.20; p 9.70 × 10-5), snoring 0.13; 2.45 10-3), sleep duration -0.11; 1.18 10-3). CPASSOC identifies 31 independent loci SRPs, including four novel loci. Functional analysis TWAS showed genes were enriched liver, brain, breast, heart tissues highlighted regulatory roles of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich chylomicron remnant positive regulation T-cell-mediated cytotoxicity pathways. Protein-protein interaction identified three potential drug target (APOE, MARK4, HLA-DRA) interacted known FDA-approved genes. demonstrated regions 11p11.2, 6p22.3, 16p11.2 may account or snoring. MR had causal effect on (ORIVW 1.02, PIVW 6.7 10-6), multivariate suggested role major depression this association. Our findings provide evidence causation abnormalities advance our understanding overlap them. Identifying targets molecular pathways can be beneficial treating disorders more efficiently.

Language: Английский

Role of sleep deprivation in immune-related disease risk and outcomes DOI Creative Commons
Sergio Garbarino, Paola Lanteri, Nicola Luigi Bragazzi

et al.

Communications Biology, Journal Year: 2021, Volume and Issue: 4(1)

Published: Nov. 18, 2021

Modern societies are experiencing an increasing trend of reduced sleep duration, with nocturnal sleeping time below the recommended ranges for health. Epidemiological and laboratory studies have demonstrated detrimental effects deprivation on Sleep exerts immune-supportive function, promoting host defense against infection inflammatory insults. has been associated alterations innate adaptive immune parameters, leading to a chronic state increased risk infectious/inflammatory pathologies, including cardiometabolic, neoplastic, autoimmune neurodegenerative diseases. Here, we review recent advancements responses as evidenced by experimental epidemiological studies, pathophysiology, role deprivation-induced changes in Gaps knowledge methodological pitfalls still remain. Further understanding causal relationship between deregulation would help identify individuals at disease prevent adverse health outcomes.

Language: Английский

Citations

325

Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease DOI Creative Commons

Zhengyun Han,

Xingmao Yang,

Shuiqing Huang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28819 - e28819

Published: April 1, 2024

Sleep deprivation refers to an intentional or unintentional reduction in sleep time, resulting insufficient sleep. It is often caused by disorders, work demands (e.g., night shifts), and study pressure. promotes Aβ deposition tau hyperphosphorylation, which a risk factor for the pathogenesis progression of Alzheimer's disease (AD). Recent research has demonstrated potential involvement both AD through glial cell activation, lymphatic system, orexin circadian rhythm inflammation, gut microbiota. Thus, investigating molecular mechanisms underlying association between crucial, may contribute development preventive therapeutic strategies AD. This review aims analyze impact on AD, exploring pathological that link initiation offers theoretical foundation drugs aimed at preventing treating

Language: Английский

Citations

8

Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates DOI Creative Commons
Gretchen T. Clark, Yanlei Yu, Cooper A. Urban

et al.

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(2), P. e1009994 - e1009994

Published: Feb. 10, 2022

Alzheimer's Disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (Aβ). AD has bi-directional relationship with circadian disruption (CD) sleep disturbances starting years before onset. However, molecular mechanism underlying CD not been elucidated. Myeloid-based phagocytosis, key component in metabolism Aβ, circadianly-regulated, presenting potential link between AD. In this work, we revealed that phagocytosis Aβ42 undergoes daily oscillation. We found timing global heparan sulfate proteoglycan (HSPG) biosynthesis was timer for clock-controlled Aβ both HSPG binding aggregation may play role These data highlight regulation immune cells intricate clock

Language: Английский

Citations

24

Towards the neurobiology of insomnia: A systematic review of neuroimaging studies DOI

Giulia Aquino,

Fee Benz, Raphael J. Dressle

et al.

Sleep Medicine Reviews, Journal Year: 2023, Volume and Issue: 73, P. 101878 - 101878

Published: Nov. 25, 2023

Language: Английский

Citations

16

Risk of neurodegenerative diseases in patients with sleep disorders: A nationwide population-based case-control study DOI
Wei Lin, Yu‐Kai Lin, Fu‐Chi Yang

et al.

Sleep Medicine, Journal Year: 2023, Volume and Issue: 107, P. 289 - 299

Published: May 19, 2023

Language: Английский

Citations

13

Aging, sex, metabolic and life experience factors: Contributions to neuro-inflammaging in Alzheimer’s disease research DOI Creative Commons

Pasindu Hansana Singhaarachchi,

Péter Antal, Frédéric Calon

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 162, P. 105724 - 105724

Published: May 16, 2024

Alzheimer's disease (AD) is prevalent around the world, yet our understanding of still very limited. Recent work suggests that cornerstone AD may include inflammation accompanies it. Failure a normal pro-inflammatory immune response to resolve lead persistent central contributes unsuccessful clearance amyloid-beta plaques as they form, neuronal death, and ultimately cognitive decline. Individual metabolic, dietary (lipid) profiles can differentially regulate this inflammatory process with aging, obesity, poor diet, early life stress other factors contributing greater risk developing AD. Here, we integrate evidence for interface between these factors, how contribute brain milieu. In particular, discuss importance appropriate polyunsaturated fatty acids (PUFA) in diet metabolism specialised pro-resolving mediators (SPMs); raising possibility strategies improve outlook.

Language: Английский

Citations

5

Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches DOI Creative Commons

Kiran Kumar Siddappaji,

Shubha Gopal

AIMS neuroscience, Journal Year: 2021, Volume and Issue: 8(3), P. 357 - 389

Published: Jan. 1, 2021

Alzheimer's disease (AD) is one of the most common, severe neurodegenerative brain disorder characterized by accumulation amyloid-beta plaques, neurofibrillary tangles in causing neural disintegration, synaptic dysfunction, and neuronal death leading to dementia. Although many US-FDA-approved drugs like Donepezil, Rivastigmine, Galantamine are available market, their consumption reduces only symptoms but fails potency cure disease. This affects individuals with aging. Combating tends be very expensive. review focuses on biochemical mechanisms neuron both at normal AD state relevance tau hypothesis, amyloid risk factors influencing dementia, oxidative stress, neuroinflammation altogether integrated neurodegeneration. A brief survey carried out biomarkers diagnosis disease, used for treatment, challenges approaching therapeutic targets inhibiting pathologies. conjointly assesses demerits inefficiency reach targets, side effects, toxicity. Optimistically, this directs advantageous strategies using nanotechnology-based drug delivery systems cross blood-brain barrier improving efficacy combined a novel stem cell therapy approach. Determinately, aims natural, non-therapeutic healing impact physical exercise different model organisms effect safe neuromodulation treatments repetitive Transcranial Magnetic Stimulation (rTMS), transcranial Electrical (tES) humans control pathologies prominent enhancing function.

Language: Английский

Citations

29

Sleep medicine: Practice, challenges and new frontiers DOI Creative Commons
Liborio Parrino, Péter Halász, Anna Szűcs

et al.

Frontiers in Neurology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

Sleep medicine is an ambitious cross-disciplinary challenge, requiring the mutual integration between complementary specialists in order to build a solid framework. Although knowledge sleep field growing impressively thanks technical and brain imaging support through detailed clinic-epidemiologic observations, several topics are still dominated by outdated paradigms. In this review we explore main novelties gaps of medicine, assess commonest disturbances, provide advices for routine clinical practice offer alternative insights perspectives on future research.

Language: Английский

Citations

19

Single-atom transition metals (Rh, Ir, Co) doped silicon carbide nanotubes (SiCNT) as nonenzymatic nitrotyrosine (NTS) sensor: Insight from theoretical calculations DOI

Gideon A. Okon,

Festus O. Ogungbemiro, Hitler Louis

et al.

Computational and Theoretical Chemistry, Journal Year: 2023, Volume and Issue: 1227, P. 114250 - 114250

Published: July 26, 2023

Language: Английский

Citations

12

Impaired sleep is associated with tau deposition on 18F-flortaucipir PET and accelerated cognitive decline, accounting for medications that affect sleep DOI
Ryan T. Kim, Liangdong Zhou, Yi Li

et al.

Journal of the Neurological Sciences, Journal Year: 2024, Volume and Issue: 458, P. 122927 - 122927

Published: Feb. 8, 2024

Language: Английский

Citations

4