Alzheimer's disease: Potential pathogenesis and imaging findings DOI Creative Commons
Yan Zhang, Chenpeng Zhang, Jianjun Liu

et al.

View, Journal Year: 2023, Volume and Issue: 4(5)

Published: May 25, 2023

Abstract Alzheimer's disease (AD) is a common neurodegenerative disease. The histopathological changes in AD include amyloid β‐protein (Aβ) deposition, tau tangles, neuroinflammation, and neurodegeneration. Some of the pathological could be shown vivo by positron emission tomography (PET) magnetic resonance imaging (MRI) biomarkers, which play key role diagnosing AD. Fluorodeoxyglucose (FDG‐PET) can reflect predict dysfunction. Aβ‐PET sensitive for diagnosis early but cannot distinguish severity Tau‐PET compensate deficiency Aβ‐PET. Tau tangles are positively correlated with associated cognitive impairment. Probes targeting neuroinflammation have been developed, further study needed to validate their effectiveness. Conventional MRI performs high tissue contrast that show structural has routinely applied clinical practice, such as evaluation cerebral atrophy. Advanced sequences (such diffusion tensor imaging, arterial spin labeling, spectroscopy, blood oxygenation level dependent, quantitative susceptibility mapping) provide additional information beyond structure includes brain microstructure, perfusion, metabolite concentration, activity, connections networks between regions, iron etc. Integrated PET may improve diagnostic efficiency

Language: Английский

Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease DOI Open Access

Nour F. Al-Ghraiybah,

Junwei Wang, Amer E. Alkhalifa

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10572 - 10572

Published: Sept. 12, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder; it the most common cause of dementia and has no treatment. It characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal Neurofibrillary tangles (NFTs). Yet, those hallmarks do not explain full pathology seen with AD, suggesting involvement other mechanisms. Neuroinflammation could offer another explanation for progression disease. This review provides an overview recent advances on role immune cells' microglia astrocytes in neuroinflammation. In become reactive several mechanisms leading to release proinflammatory cytokines that further neuronal damage. We then provide updates neuroinflammation diagnostic markers investigational therapeutics currently clinical trials target

Language: Английский

Citations

91
Dissecting the clinical heterogeneity of early-onset Alzheimer’s disease DOI Creative Commons
Daniel W. Sirkis, Luke W. Bonham, Taylor P. Johnson

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(6), P. 2674 - 2688

Published: April 7, 2022

Abstract Early-onset Alzheimer’s disease (EOAD) is a rare but particularly devastating form of AD. Though notable for its high degree clinical heterogeneity, EOAD defined by the same neuropathological hallmarks underlying more common, late-onset In this review, we describe various syndromes associated with EOAD, including typical amnestic phenotype as well atypical variants affecting visuospatial, language, executive, behavioral, and motor functions. We go on to highlight advances in fluid biomarker research how molecular, structural, functional neuroimaging can be used not only improve diagnostic acumen also enhance our understanding fundamental pathobiological changes occurring years (and even decades) before onset symptoms. addition, discuss genetic variation pathogenic responsible well-known mendelian forms that may increase risk much common are either considered sporadic or lack clear autosomal-dominant inheritance pattern. Intriguingly, specific PRNP MAPT —genes which commonly other neurodegenerative diseases—may provide unexpectedly important insights into formation AD tau pathology. Genetic analysis will continue challenging given their rarity, integration data, multimodal imaging, ‘omics techniques application study large, multicenter cohorts enable future discoveries mechanisms development varied presentations.

Language: Английский

Citations

89
Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders DOI Creative Commons
Jessica R. Cohen,

Annette Mathew,

Kirk D. Dourvetakis

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 511 - 511

Published: March 14, 2024

Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s (PD), traumatic brain injury (TBI) Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions these pathogeneses is currently not clearly understood. These show dysregulated inflammatory responses, activation neurons, glial cells, neurovascular unit damage associated with excessive release proinflammatory cytokines, chemokines, neurotoxic mediators, infiltration peripheral immune cells into brain, as well entry mediators through damaged endothelial blood–brain barrier tight junction proteins. Activation leads to many molecules that cause neuroinflammation neurodegeneration. Gulf War Illness (GWI) myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) also dysfunctions. Currently, there no effective disease-modifying therapeutic options available for diseases. Human induced pluripotent stem cell (iPSC)-derived astrocytes, microglia, pericytes used models drug discovery. This review highlights certain recent trends in neuroinflammatory responses iPSC-derived applications

Language: Английский

Citations

29
Neuroinflammation as a Potential Therapeutic Target in Alzheimer’s Disease DOI Creative Commons
Ping Liu, Yunyun Wang, Yan Sun

et al.

Clinical Interventions in Aging, Journal Year: 2022, Volume and Issue: Volume 17, P. 665 - 674

Published: April 1, 2022

Abstract: Although amyloid-β (Aβ) peptide accumulation is considered as a key early event in the pathogenesis of Alzheimer’s disease (AD), precise pathophysiology this deadly illness remains unclear and no effective remedies capable inhibiting progression have been discovered. In addition to deposition extracellular Aβ plaques intracellular neurofibrillary tangles, neuroinflammation has identified third core characteristic crucial AD. More more evidence from laboratory clinical studies suggested that anti-inflammatory treatments could defer or prevent occurrence review, we will discuss multifaceted presented AD newly emerged targets both pre-clinical Keywords: disease, neuroinflammation, disease‐modifying therapy, treatment

Language: Английский

Citations

54
Multipronged diagnostic and therapeutic strategies for Alzheimer's disease DOI Creative Commons
Madhu Ramesh, Thimmaiah Govindaraju

Chemical Science, Journal Year: 2022, Volume and Issue: 13(46), P. 13657 - 13689

Published: Jan. 1, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and major contributor to dementia cases worldwide. AD clinically characterized by learning, memory, cognitive deficits. The accumulation of extracellular amyloid β (Aβ) plaques neurofibrillary tangles (NFTs) tau are the pathological hallmarks explored as targets for clinical diagnosis therapy. pathology poorly understood there no fully approved treatments. Notwithstanding gap, decades research in understanding mechanisms have revealed multifactorial nature AD. As result, multipronged holistic approaches pertinent targeting multiple biomarkers developing effective therapeutics. In this perspective, recent developments Aβ targeted diagnostic therapeutic tools discussed. Novel indirect, combination, circulating potential highlighted. We underline importance multiplexing multimodal detection generate biomarker fingerprints reliable strategy. classical therapeutics aggregation pathways described with bottlenecks Drug discovery efforts multifaceted toxicity involving protein aggregation, metal toxicity, oxidative stress, mitochondrial damage, neuroinflammation Recent focused on strategies rationally design multifunctional modulators factors presented future drug development discover

Language: Английский

Citations

52
Current trends in blood biomarker detection and imaging for Alzheimer’s disease DOI
Shun Hu, Changwen Yang, Haiming Luo

et al.

Biosensors and Bioelectronics, Journal Year: 2022, Volume and Issue: 210, P. 114278 - 114278

Published: April 13, 2022

Language: Английский

Citations

50
Rapamycin Attenuated Zinc-Induced Tau Phosphorylation and Oxidative Stress in Rats: Involvement of Dual mTOR/p70S6K and Nrf2/HO-1 Pathways DOI Creative Commons

Chencen Lai,

Zhuyi Chen,

Yuanting Ding

et al.

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

Published: Feb. 7, 2022

Alzheimer's disease is pathologically characterized by abnormal accumulation of amyloid-beta plaques, neurofibrillary tangles, oxidative stress, neuroinflammation, and neurodegeneration. Metal dysregulation, including excessive zinc released presynaptic neurons, plays an important role in tau pathology oxidase activation. The activities mammalian target rapamycin (mTOR)/ribosomal S6 protein kinase (p70S6K) are elevated the brains patients with disease. Zinc induces hyperphosphorylation

Language: Английский

Citations

39
Microglia-Astrocyte Communication in Alzheimer’s Disease DOI Creative Commons
Yingying Wu, Ulrich Eisel

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 95(3), P. 785 - 803

Published: Aug. 25, 2023

Microglia and astrocytes are regarded as active participants in the central nervous system under various neuropathological conditions, including Alzheimer's disease (AD). Both microglia astrocyte activation have been reported to occur with a spatially temporarily distinct pattern. Acting double-edged sword, glia-mediated neuroinflammation may be both detrimental beneficial brain. In variety of neuropathologies, activated before astrocytes, which facilitates activation. Yet reactive can also prevent adjacent addition helping them become activated. Studies describe changes genetic profile well cellular molecular responses these two types glial cells that contribute dysfunctional immune crosstalk AD. this paper, we construct current knowledge microglia-astrocyte communication, highlighting multifaceted functions their role A thorough comprehension communication could hasten creation novel AD treatment approaches.

Language: Английский

Citations

36
Brain and Systemic Inflammation in De Novo Parkinson's Disease DOI Creative Commons
Talene A. Yacoubian, Yu-Hua Fang, Adam Gerstenecker

et al.

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(5), P. 743 - 754

Published: Feb. 28, 2023

To assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson's disease (PD).Evidence for a pathophysiologic role PD is growing. However, several key gaps remain as to PD, including extent immune activation at early stages, potential effects treatments on whether pro-inflammatory signals are associated clinical features and/or predict more rapid progression.We enrolled de novo (n = 58) age-matched controls 62). Subjects underwent assessments, Movement Disorder Society-United Disease rating scale (MDS-UPDRS). Comprehensive cognitive assessment meeting MDS Level II criteria mild impairment testing was performed. Blood obtained flow cytometry cytokine/chemokine analyses. imaging 18 F-DPA-714, translocator protein 18kd ligand, lumbar puncture if eligible consented.Baseline demographics medical history were comparable between groups. showed significant differences University Pennsylvania Smell Identification Test, Schwab England Activities Daily Living, Scales Outcomes autonomic dysfunction, MDS-UPDRS scores. Cognitive demonstrated composite, executive function, visuospatial domain scores baseline. Positron emission tomography increased F-DPA-714 signal subjects. correlated measures some chemokines.18 central compared controls. Longitudinal follow-up will be important determine predicts decline. © 2023 The Authors. Disorders published by Wiley Periodicals LLC behalf International Parkinson Society.

Language: Английский

Citations

32
Pain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions DOI Open Access

Martina Favretti,

Cristina Iannuccelli, Manuela Di Franco

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10443 - 10443

Published: June 21, 2023

Fibromyalgia is a complex and heterogeneous clinical syndrome, mainly characterized by the presence of widespread pain, possibly associated with variety other symptoms. can have an extremely negative impact on psychological, physical social lives people affected, sometimes causing patients to experience dramatically impaired quality life. Nowadays, diagnosis fibromyalgia still clinical, thus favoring diagnostic uncertainties making its clear identification challenging establish, especially in primary care centers. These difficulties lead undergo innumerable visits, investigations specialist consultations, increasing their stress, frustration even dissatisfaction. Unfortunately, research over last 25 years regarding specific biomarker for has been fruitless. The discovery reliable syndrome would be critical step towards early this condition, not only reducing patient healthcare utilization test execution but also providing intervention guideline-based treatments. This narrative article reviews different metabolite alterations proposed as possible biomarkers fibromyalgia, focusing associations evidence highlights some new, promising areas context. Nevertheless, none analyzed metabolites emerge sufficiently validated biomarker. Given complexity future, panel biomarkers, including subtype-specific could considered interesting alternative area.

Language: Английский

Citations

26