Identification of immune microenvironment subtypes and signature genes for Alzheimer’s disease diagnosis and risk prediction based on explainable machine learning DOI Creative Commons

Yongxing Lai,

Peiqiang Lin,

Fan Lin

et al.

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

Published: Dec. 8, 2022

Background Using interpretable machine learning, we sought to define the immune microenvironment subtypes and distinctive genes in AD. Methods ssGSEA, LASSO regression, WGCNA algorithms were used evaluate state AD patients. To predict fate of identify genes, six learning developed. The output models was interpreted using SHAP LIME algorithms. For external validation, four separate GEO databases used. We estimated subgroups immunological unsupervised clustering. Further research done on variations microenvironment, enhanced functions pathways, therapeutic medicines between these subtypes. Finally, expression characteristic verified AlzData pan-cancer RT-PCR analysis. Results It determined that is connected changes microenvironment. revealed 31 potential which greenyellow blue modules shown be most associated with infiltrated cells. In testing set, XGBoost algorithm had best performance an AUC 0.86 a P-R value 0.83. Following screening set by verification independent datasets, five (CXCR4, PPP3R1, HSP90AB1, CXCL10, S100A12) closely pathological biomarkers allowed for accurate prediction progression found microenvironment-related genes. feature gene-based nomogram may provide clinical advantages Two patients identified, subtype2 linked metabolic phenotype, subtype1 belonged immune-active kind. MK-866 arachidonyltrifluoromethane identified as top treatment agents 1 2, respectively. These distinguishing intimately development disease, according Alzdata database, research, Conclusion hub are strongly pathology CXCR4, S100A12. hypothesized molecular might offer novel perceptions individualized treatment.

Language: Английский

Retinal pathological features and proteome signatures of Alzheimer’s disease DOI Creative Commons

Yosef Koronyo,

Altan Rentsendorj, Nazanin Mirzaei

et al.

Acta Neuropathologica, Journal Year: 2023, Volume and Issue: 145(4), P. 409 - 438

Published: Feb. 11, 2023

Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly early stages of functional impairment, how they relate to progression brain remain largely unknown. To better understand pathological features AD retina, we conducted an extensive histopathological biochemical investigation postmortem retina tissues from 86 human donors. Quantitative examination superior inferior temporal retinas mild cognitive impairment (MCI) patients compared those with normal cognition (NC) revealed significant increases amyloid β-protein (Aβ

Language: Английский

Citations

82
CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer’s disease pathology DOI
Wei Su, Jordy Saravia, Isabel Risch

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(10), P. 1735 - 1747

Published: Sept. 7, 2023

Language: Английский

Citations

79
Current understanding of the Alzheimer’s disease-associated microbiome and therapeutic strategies DOI Creative Commons
Dong-oh Seo, David M. Holtzman

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(1), P. 86 - 94

Published: Jan. 4, 2024

Abstract Alzheimer’s disease (AD) is a fatal progressive neurodegenerative disease. Despite tremendous research efforts to understand this complex disease, the exact pathophysiology of not completely clear. Recently, anti-Aβ antibodies have been shown remove amyloid from brain and slow clinical progression mild dementia by ~30%. However, exploring alternative strategies crucial understanding developing more effective therapeutic interventions. In recent years, microbiota-gut-brain axis has received significant attention in AD field. Numerous studies suggested that alterations gut microbiota composition are associated with AD, several underlying mechanisms proposed. area still their infancy, many aspects field just beginning be explored understood. Gaining deeper intricate interactions signaling pathways involved microbiota-AD interaction for optimizing targeting positively impact AD. review, we aim summarize current We will discuss existing evidence regarding role pathogenesis, mechanisms, biological factors influencing microbiome-gut-brain remaining questions Last, potential approaches recondition community alleviate progression. An ongoing exploration gut-brain development microbiota-based therapies hold advancing management future.

Language: Английский

Citations

78
Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications DOI Creative Commons
Saleh Hadi Alharbi

Therapeutic Advances in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have emerged as promising therapeutic agents with potent anti-inflammatory properties and diverse clinical implications. This in-depth review article explores the mechanisms behind actions of GLP-1RAs assesses their prospective applicability in a wide range disease scenarios. The current establishes significance comprehending role identifies pertinent research gaps. A concise overview inflammation its consequences underscores critical need for effective interventions. Subsequently, elucidates intricate through which modulate immune cell signaling regulate nuclear factor-kappa B (NF-κB) pathway. Detailed discussions encompass impact on inflammatory responses, cytokine production, attenuation oxidative stress. exposition is substantiated by collection examples an extensive array references from both preclinical investigations. historical trajectory GLP-1RA drugs, including exenatide, lixisenatide, liraglutide, semaglutide, traced to delineate development agents. Moreover, emphasizes potential specific contexts like type 2 diabetes, neurodegenerative disorder, bowel (IBD), shedding light effects rigorous examination studies. also provides outlook future perspectives GLP-1RAs, encompassing domains diseases, IBD. In conclusion, exhibit substantial effects, rendering them broad They are very useful variety diseases because they immunological block NF-κB activation, decrease production pro-inflammatory cytokines. Ongoing endeavors aim optimize use, patient-specific treatment paradigms, explore novel applications. represent significant breakthrough therapy, offering options, improved patient outcomes.

Language: Английский

Citations

68
The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson’s disease DOI Creative Commons
Aurélie de Rus Jacquet, Melanie Alpaugh, Hélèna L. Denis

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 20, 2023

Abstract Astrocyte dysfunction has previously been linked to multiple neurodegenerative disorders including Parkinson’s disease (PD). Among their many roles, astrocytes are mediators of the brain immune response, and astrocyte reactivity is a pathological feature PD. They also involved in formation maintenance blood-brain barrier (BBB), but integrity compromised people with This study focuses on an unexplored area PD pathogenesis by characterizing interplay between astrocytes, inflammation BBB integrity, combining patient-derived induced pluripotent stem cells microfluidic technologies generate 3D human chip. Here we report that derived from female donors harboring PD-related LRRK2 G2019S mutation pro-inflammatory fail support functional capillary vitro. We show inhibition MEK1/2 signaling attenuates inflammatory profile mutant rescues formation, providing insights into mechanisms regulating Lastly, confirm vascular changes observed postmortem substantia nigra both males females

Language: Английский

Citations

54
Complement in the Brain: Contributions to Neuroprotection, Neuronal Plasticity, and Neuroinflammation DOI Creative Commons
Suzanne S. Bohlson, Andrea J. Tenner

Annual Review of Immunology, Journal Year: 2023, Volume and Issue: 41(1), P. 431 - 452

Published: Feb. 8, 2023

The complement system is an ancient collection of proteolytic cascades with well-described roles in regulation innate and adaptive immunity. With the convergence a revolution complement-directed clinical therapeutics, discovery specific complement-associated targetable pathways central nervous system, development integrated multi-omic technologies that have all emerged over last 15 years, precision therapeutic targeting Alzheimer disease other neurodegenerative diseases processes appears to be within reach. As sensor tissue distress, protects brain from microbial challenge as well accumulation dead and/or damaged molecules cells. Additional more recently discovered diverse functions make it paramount importance design neurotherapeutics such beneficial neurodevelopment, adult neural plasticity, neuroprotective are retained.

Language: Английский

Citations

47
Chronic effects of inflammation on tauopathies DOI

Connor Langworth-Green,

Saisha Patel,

Zane Jaunmuktane

et al.

The Lancet Neurology, Journal Year: 2023, Volume and Issue: 22(5), P. 430 - 442

Published: April 13, 2023

Language: Английский

Citations

43
Inflammatory aspects of Alzheimer’s disease DOI
Pablo Botella Lucena, Michael T. Heneka

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Aug. 28, 2024

Language: Английский

Citations

25
Peripheral blood amyloid-β involved in the pathogenesis of Alzheimer’s disease via impacting on peripheral innate immune cells DOI Creative Commons
Mingchao Shi, Fengna Chu, Feiqi Zhu

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 4, 2024

A key pathological factor of Alzheimer's disease (AD), the most prevalent form age-related dementia in world, is excessive β-amyloid protein (Aβ) extracellular aggregation brain. And peripheral blood, a large amount Aβ derived from platelets. So far, causality between levels blood and its brain, particularly role pathology AD, still unclear. relation tau tangles another crucial pathologic contributing to pathogenesis also ambiguous. More recently, anti-Aβ monoclonal antibodies are approved for treatment AD patients through declining mechanism action enhance plasma central nervous system (CNS) clearance, leading decrease burden brain improving cognitive function, which clearly indicates that impacted on involved AD. In addition, innate immune cells remains mostly unknown results obtained were controversial. present review, we summarize recent studies roles Finally, based published data our own work, believe plays an important development progression by impacting cells.

Language: Английский

Citations

22
Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease DOI Creative Commons
Renqing Zhao

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Feb. 2, 2024

Abstract Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD), characterized by the stimulation resident immune cells brain and penetration peripheral cells. These inflammatory processes facilitate deposition amyloid-beta (Aβ) plaques abnormal hyperphosphorylation tau protein. Managing neuroinflammation to restore homeostasis decrease neuronal damage therapeutic approach for AD. One way achieve this through exercise, which can improve function protect against neuroinflammation, oxidative stress, synaptic dysfunction in AD models. The neuroprotective impact exercise regulated various molecular factors that be activated same as administration their mimetics. Recent evidence has proven some mimetics effective alleviating AD, and, additionally, they are helpful alternative option patients who unable perform regular physical manage neurodegenerative disorders. This review focuses on current state knowledge mimetics, including efficacy, regulatory mechanisms, progress, challenges, limitations, future guidance application therapy.

Language: Английский

Citations

19