Combined analysis of single-cell and bulk RNA sequencing reveals the expression patterns of circadian rhythm disruption in the immune microenvironment of Alzheimer's disease

Article Immunology

Interleukin-17 Promotes the Infiltration of CD8+T Cells into the Brain in a Mouse Model for Alzheimer's Disease

Xiaoyang Ye et al.

Summary: IL-17 signaling promotes neuroinflammation in Alzheimer's disease by accelerating the infiltration of CD8+ T lymphocytes and Gr1+ CD11b+ myeloid cells.

IMMUNOLOGICAL INVESTIGATIONS (2023)

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Article Clinical Neurology

Progranulin mutations in clinical and neuropathological Alzheimer's disease

Badri N. Vardarajan et al.

Summary: This study found that pathogenic GRN mutations are common in FTLD and AD, often with TDP-43 pathology. Pathogenic GRN carriers have significantly higher PHFtau tangle density associated with AD. The rs5848 mutation is associated with increased frequency of hippocampal sclerosis and TDP-43 deposits in AD patients.

ALZHEIMERS & DEMENTIA (2022)

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Article Clinical Neurology

Chronic sleep deprivation altered the expression of circadian clock genes and aggravated Alzheimer's disease neuropathology

Long Niu et al.

Summary: Chronic sleep deprivation impaired learning and memory, exacerbating disease progression in Alzheimer's disease (AD) mice. Abnormal expression of clock genes in the circadian rhythm-related nuclei, especially in AD mice, was found after chronic sleep deprivation. Moreover, abnormal tau phosphorylation was accompanied by alterations in BMAL1 protein levels in the retrosplenial cortex.

BRAIN PATHOLOGY (2022)

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Review Clinical Neurology

Circadian rhythms in neurodegenerative disorders

Malik Nassan et al.

Summary: The circadian system governs physiological processes like sleep, alertness, and cognition, and disruptions in circadian homeostasis can have detrimental effects on human health, especially in neurodegenerative disorders. There is a bidirectional relationship between circadian function and neurodegeneration, highlighting the importance of studying circadian disruption in these disorders. Research in this field could lead to novel circadian-based therapeutic interventions for disabling conditions like Parkinson's, Alzheimer's, and other neurodegenerative diseases.

NATURE REVIEWS NEUROLOGY (2022)

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Article Multidisciplinary Sciences

Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer

Zaoqu Liu et al.

Summary: The study developed a machine learning-based method to predict prognosis, recurrence, and treatment benefits in colorectal cancer patients, and constructed an immune-related long non-coding RNA signature.

NATURE COMMUNICATIONS (2022)

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Article Biology

A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

Chen Yang et al.

Summary: Pharmacologic perturbation projects have generated expression data for computational therapeutic discovery, but optimal methodologies and parameters are still unclear. This study developed benchmarking standards and determined an optimal approach for drug retrieval. The candidate agent HHT was validated and shown to have therapeutic effects on liver cancer.

ELIFE (2022)

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Article Endocrinology & Metabolism

Single-cell transcriptomic analysis reveals circadian rhythm disruption associated with poor prognosis and drug-resistance in lung adenocarcinoma

Lei He et al.

Summary: This study developed a computational framework called CRDscore to define the intratumoral status of circadian disruption in lung adenocarcinoma using single-cell transcriptomic data. The study found that malignant cells with high CRDscore exhibited activation of glycolysis and epithelial-mesenchymal transition pathways. Additionally, CRD played a crucial role in T cell exhaustion, which was associated with poor prognosis. Cox regression analysis also showed that CRDscore was a valuable prognostic biomarker.

JOURNAL OF PINEAL RESEARCH (2022)

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Review Clinical Neurology

T Cells: A Growing Universe of Roles in Neurodegenerative Diseases

Dallin Dressman et al.

Summary: T cells play a central role in homeostasis and host defense against infectious diseases. Dysregulation of T cells can lead to autoimmune responses. T cells are also involved in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease, potentially interacting with microglia in shaping the inflammatory cascade.

NEUROSCIENTIST (2022)

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Review Geriatrics & Gerontology

Post-translational Modifications of the p53 Protein and the Impact in Alzheimer's Disease: A Review of the Literature

James S. Clark et al.

Summary: This review explores the role of p53 protein in Alzheimer's disease (AD), particularly its impact on protein function through post-translational modifications (PTMs) and its relevance to AD pathogenesis. In-depth understanding of p53's involvement in AD could lead to more targeted therapies for patients with this debilitating disease.

FRONTIERS IN AGING NEUROSCIENCE (2022)

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Review Biochemistry & Molecular Biology

The Pivotal Role of NF-kB in the Pathogenesis and Therapeutics of Alzheimer's Disease

Emily Sun et al.

Summary: This review provides an overview of the role of NF-kappa B in the pathogenesis of Alzheimer's Disease (AD), including its interaction with various molecular factors in AD models, neurons, and glial cells. With the multifactorial nature of AD development and the failure of many drugs, targeting the NF-kappa B signaling pathway may generate widespread interest in AD research and provide more therapeutic options for AD patients.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Immunology

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

Yongxing Lai et al.

Summary: Using interpretable machine learning, this study identified immune microenvironment subtypes and distinctive genes in AD. Machine learning algorithms were used to predict AD progression and identify related genes. The study found five immune microenvironment-related genes closely associated with AD pathology. Two immune microenvironment subgroups for AD patients were identified, with one linked to a metabolic phenotype and the other belonging to the immune-active type. The findings provide insights for personalized AD treatment.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Immunology

Necroptosis Identifies Novel Molecular Phenotypes and Influences Tumor Immune Microenvironment of Lung Adenocarcinoma

Chen Zhao et al.

Summary: This study investigates the immune and epigenetic mutational landscape of necroptosis in LUAD and develops a prognostic scoring system to predict patient outcomes and treatment responses.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Oncology

Circadian Rhythm Disruption as a Contributor to Racial Disparities in Prostate Cancer

Sonali S. Dasari et al.

Summary: This study discusses the relationship between circadian rhythm disruption and racial disparities in African American prostate cancer, emphasizing the importance of integrating circadian-related therapies to improve current treatment methods for prostate cancer.

CANCERS (2022)

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Review Cell Biology

Insights into T-cell dysfunction in Alzheimer's disease

Linbin Dai et al.

Summary: Research suggests that dysfunctional T cells and neuroinflammation play critical roles in Alzheimer's disease pathology, with T cells contributing indirectly to neuroinflammation by secreting proinflammatory mediators. Risk factors and pathological hallmarks of AD are closely linked to immune responses, potentially influencing T cell function.

AGING CELL (2021)

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Review Clinical Neurology

APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches

Alberto Serrano-Pozo et al.

Summary: The APOE ε4 allele and ε2 allele are respectively the strongest genetic risk factor and protective factor for Alzheimer's disease. While therapies targeting APOE are currently unavailable, recent research has expanded our understanding of APOE pathogenesis to include multiple pathological processes, offering valuable insights for therapy development.

LANCET NEUROLOGY (2021)

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Review Neurosciences

Role of Hypoxia Inducible Factor-1α in Alzheimer's Disease

Yang-Yang Wang et al.

Summary: HIF-1 alpha plays a dual role in Alzheimer's disease, both promoting pathological development and resisting pathogenic effects, making it a complex factor with potential therapeutic implications.

JOURNAL OF ALZHEIMERS DISEASE (2021)

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Article Genetics & Heredity

NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1

Yang Shen et al.

Summary: Recent studies have shown that NF-kappa B plays a significant role in directly regulating the circadian clock, altering clock oscillations in both cells and tissues, as well as in mice. NF-kappa B competes with coregulators like CRY1 and CBP/p300 for BMAL1 binding to affect circadian transcription, linking inflammation to circadian timekeeping.

PLOS GENETICS (2021)

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Article Cell Biology

The role of mitophagy in the regulation of mitochondrial energetic status in neurons

Sinsuk Han et al.

Summary: Mitochondria are crucial for supplying energy to neurons, and dysfunction in these organelles is associated with early features of Alzheimer's disease (AD). In AD, metabolic and mitochondrial disruptions occur before clinical symptoms, and mitophagy, a process of clearing damaged mitochondria, plays a role in maintaining energy metabolism and synaptic function. However, in AD mouse models, early stimulation of mitochondrial activity can worsen synaptic loss due to impaired mitophagy. Enhancing lysosomal function restores metabolic function and protects against synaptic damage in AD. This research suggests that targeting mitophagy and lysosomal activity may offer potential therapeutic strategies for AD.

AUTOPHAGY (2021)

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Article Multidisciplinary Sciences

Therapeutic B-cell depletion reverses progression of Alzheimer's disease

Ki Kim et al.

Summary: The study demonstrates that accumulation of activated B cells is crucial to the pathology of AD in three relevant transgenic animal models, and depletion of B cells interferes with both histological and behavioral manifestations of the disease.

NATURE COMMUNICATIONS (2021)

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Review Cell Biology

The role of the immune system in Alzheimer's disease

Kai-Min Wu et al.

Summary: Alzheimer's disease is characterized by the accumulation of amyloid plaques and tau tangles, with increasing evidence suggesting that the immune system plays a vital role in AD etiology and pathogenesis. The recognition of misfolded proteins by immune cells can lead to neuroinflammation and neurodegeneration, while genetic susceptibility and other immune-related factors also contribute to AD development. Further research on immune cell alterations, gene susceptibility, and immune-related mechanisms may provide new insights for potential immunotherapies and biomarkers for AD.

AGEING RESEARCH REVIEWS (2021)

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Article Immunology

Andrographolide ameliorates neuroinflammation in APP/PS1 transgenic mice

Jiawei Zhang et al.

Summary: Andrographolide can significantly alleviate cognitive impairments, reduce amyloid-β deposition, inhibit microglial activation, and decrease the secretion of proinflammatory factors in APP/PS1 mice. Furthermore, transcriptome sequencing analysis revealed that Andro could significantly decrease the expression of various genes associated with inflammation in APP/PS1 mice, which was further validated by qRT-PCR. Our results suggest that Andro might be a potential therapeutic drug for AD by regulating neuroinflammation.

INTERNATIONAL IMMUNOPHARMACOLOGY (2021)

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Review Biochemistry & Molecular Biology

When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer's and Huntington's Disease

Santosh R. D'Mello

Summary: Alzheimer's disease and Huntington's disease are characterized by cognitive decline and motor abnormalities respectively, with both conditions involving abnormal actions of common kinases. Research into these kinases may lead to more effective therapeutic approaches for these neurodegenerative diseases.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Gastroenterology & Hepatology

Sleep, circadian rhythm and gut microbiota: alterations in Alzheimer's disease and their potential links in the pathogenesis

Yi Li et al.

Summary: Recent studies have shown alterations in gut microbiota in Alzheimer's disease patients, as well as a correlation between sleep and circadian rhythm disruption and greater beta-amyloid deposition and AD risk. These studies aim to identify commonalities and distinct characteristics of GM alterations in these conditions, and their impact on pathophysiology.

GUT MICROBES (2021)

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Review Clinical Neurology

Circadian Rhythm Sleep-Wake Disorders: a Contemporary Review of Neurobiology, Treatment, and Dysregulation in Neurodegenerative Disease

Tyler A. Steele et al.

Summary: Circadian rhythms play a crucial role in various physiological processes and daily life activities. Different circadian sleep-wake disorders require specific management strategies, such as light therapy, melatonin, and other pharmacological treatments.

NEUROTHERAPEUTICS (2021)

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Article Clinical Neurology

2021 Alzheimer's disease facts and figures

[Anonymous]

Summary: Alzheimer's disease has a significant impact on individuals and society as a whole, with a large number of patients in the United States and a potential for continued growth in the future. The value of unpaid caregivers has increased despite a decline in their numbers, and healthcare costs are on the rise. Racial and ethnic disparities in healthcare persist, highlighting the need for greater diversity in dementia care workforce and clinical trials.

ALZHEIMERS & DEMENTIA (2021)

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Correction Clinical Neurology

APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches (vol 20, pg 68, 2021)

Alberto Serrano-Pozo et al.

LANCET NEUROLOGY (2021)

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Review Biochemistry & Molecular Biology

Molecular Interactions Between Components of the Circadian Clock and the Immune System

Sophia Hergenhan et al.

JOURNAL OF MOLECULAR BIOLOGY (2020)

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Article Immunology

CD8+ T-cells infiltrate Alzheimer's disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice

M. S. Unger et al.

BRAIN BEHAVIOR AND IMMUNITY (2020)

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Restoration of L-OPA1 alleviates acute ischemic stroke injury in rats via inhibiting neuronal apoptosis and preserving mitochondrial function

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Effects of Housing Conditions and Circadian Time on Baseline c-Fos Immunoreactivity in C57BL/6J Mice

Meridith T. Robins et al.

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Drugs Modulating CD4+T Cells Blood-Brain Barrier Interaction in Alzheimer's Disease

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The single-cell transcriptional landscape of mammalian organogenesis

Junyue Cao et al.

NATURE (2019)

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Treatment Combinations for Alzheimer's Disease: Current and Future Pharmacotherapy Options

Jeffrey L. Cummings et al.

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Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas

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Perturbation-response genes reveal signaling footprints in cancer gene expression

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Expression of the Circadian Clock Gene BMAL1 Positively Correlates With Antitumor Immunity and Patient Survival in Metastatic Melanoma

Leonardo Vinicius Monteiro de Assis et al.

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IL-1β, IL-6, TNF-α and CRP in Elderly Patients with Depression or Alzheimer's disease: Systematic Review and Meta-Analysis

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JunB regulates homeostasis and suppressive functions of effector regulatory T cells

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T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis

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Circadian Rhythm Disruption Promotes Lung Tumorigenesis

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Drug treatments in Alzheimer's disease

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Genetic diagnosis and prognosis of Alzheimer's disease: challenges and opportunities

Christiane Reitz

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Aβ-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer's disease

Hyundong Song et al.

MOLECULAR NEURODEGENERATION (2015)

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Amyloid-β and Tau The Trigger and Bullet in Alzheimer Disease Pathogenesis

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CD4 T cells in immunity and immunotherapy of Alzheimer's disease

Alon Monsonego et al.

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Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Erik S. Musiek et al.

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Acceleration of the Development of Alzheimer's Disease in Amyloid Beta-Infused Peroxiredoxin 6 Overexpression Transgenic Mice

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MOLECULAR NEUROBIOLOGY (2013)

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CircaDB: a database of mammalian circadian gene expression profiles

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Evidence for circadian regulation of activating transcription factor 5 but not tyrosine hydroxylase by the chromaffin cell clock

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Frontline: ICER/CREM-mediated transcriptional attenuation of IL-2 and its role in suppression by regulatory T cells

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EUROPEAN JOURNAL OF IMMUNOLOGY (2007)

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Combined analysis of single-cell and bulk RNA sequencing reveals the expression patterns of circadian rhythm disruption in the immune microenvironment of Alzheimer's disease

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