The Role of Immunosenescence in Neurodegenerative Diseases

Costantini, Erica; D’Angelo, Chiara; Reale, Marcella

doi:10.1155/2018/6039171

Cited by 97 publications

(84 citation statements)

References 124 publications

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“…This compositional shift in the CD4+ Tcell population might have occurred because of reduced thymopoiesis or because of repeated exposure of na€ ıve cells to antigens [16,17]. Accordingly, aging is accompanied by a contraction of the peripheral na€ ıve CD4+ T-cell repertoire, with poor responsiveness to new antigens [18]. To better distinguish true na€ ıve and memory cells, we also analysed the expression of CD45RA and CD45RO, with na€ ıve cells and terminally differentiated T cells more likely to express CD45RA, and memory and activated T cells more likely to express CD45RO [19,20].…”

Section: Discussionmentioning

confidence: 99%

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

D’Angelo

Goldeck

Pawelec

et al. 2020

Euro J of Neurology

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Background and purpose The differentiation of Alzheimer’s disease (AD) dementia from vascular dementia (VaD) and mixed‐type dementia (mixed dementia) requires stepwise analysis and usually occurs late in the disease process. Early diagnosis and therapy monitoring would benefit greatly from the identification of biomarkers of neurodegeneration, especially blood biomarkers. To this end, the aim of the present pilot study was to investigate differences in the distribution of peripheral T‐cell populations in patients with AD compared to VaD and mixed dementia. Methods Flow cytometry was performed on blood samples from 11 patients with AD, six with VaD and six with mixed dementia, as well as 17 healthy control subjects (HCs). CD4+ and CD8+ T cells were typed for expression of CD45, CD27, CD28, CD25, FoxP3, CCR4 and CCR6; the other leukocytes were also assessed. Functionally, immune cell uptake of the β‐amyloid (Aβ) toxic fragment (Aβ1–42) was also evaluated. Results A higher proportion of CD4+CD28− memory T cells and a reciprocal reduction of CD4+CD28+CD27+ naïve T lymphocytes was detected in all patient groups relative to controls. Significantly fewer CD4+CD25+FoxP3 regulatory T cells were present in patients with VaD, and significantly more CCR6+ and CCR4+ CD4+ T cells in those with AD. Higher CCR6+ T‐cell frequencies were also present in patients with mixed dementia, potentially due to the inflammation and immune cell chemoattraction triggered by Aβ. Conclusions The present study was a comprehensive investigation comparing different kinds of dementia, revealing differentially expressed peripheral markers that are potentially useful for early AD, VaD and mixed dementia diagnoses, and that would assist in proper treatments for these disparate diseases. Validation is now required.

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Section: Discussionmentioning

confidence: 99%

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

D’Angelo

Goldeck

Pawelec

et al. 2020

Euro J of Neurology

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“…La menor eficiencia y capacidad de respuesta de la inmunidad innata en edad avanzada es un hecho que aporta vulnerabilidad frente a una infección [27]. Son diversos los estudios que sugieren que el aumento del entorno proinflamatorio contribuye al desarrollo de enfermedades asociadas a la edad, demostrándose una relación entre la inmunosenescencia y su contribución a la neuroinflamación y el consiguiente desarrollo de la patología neurodegenerativa, como, por ejemplo, ocurre en la Enfermedad de Alzheimer donde la disfunción microglial conlleva a una acumulación de Aβ conducente a pérdida de respuesta inmune periférica [28] Todo ello nos lleva a la conclusión de que el Sistema Nervioso, tanto a nivel central como periférico, puede considerarse como una diana preferente de los mecanismos neuroinflamatorios, con especial interés en la influencia que esta infección pudiera tener sobre la puesta en marcha o la progresión de Enfermedades Neurodegenerativas.…”

Section: Tormenta De Citoquinas Y Sistema Nerviosounclassified

Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?

et al. 2020

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INTRODUCCIÓN: La infección por el coronavirus SARS-CoV2 originada en Diciembre de 2019 en la región china de Wuhan ha adquirido proporciones pandémicas. A día de hoy ha ocasionado de Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic?ABSTRACT Introduction: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium-and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. Development:We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system.Conclusions: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.

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“…The potential changes in the immunopathological mechanisms of MS with ageing are wideranging 66 . A comprehensive discussion of this complex and poorly understood area is beyond the scope of this Review, but two general and seemingly contradictory aspects are important to highlight.…”

Section: {H2} Ageing and Inflammationmentioning

confidence: 99%

Chronic inflammation in multiple sclerosis — seeing what was always there

Matthews

2019

Nat Rev Neurol

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• Advanced MRI and PET methods enable visualization of features related to chronic inflammation in progressive and relapsing-remitting forms of multiple sclerosis (MS). • Quantitative analysis of uptake of gadolinium contrast agent and ultra-small paramagnetic particles provide in vivo evidence of chronic, low-grade inflammation in people with progressive or relapsing-remitting MS. • Lesions associated with activated macrophages/microglia (slowly expanding T2 hyperintense lesions and lesions with high susceptibility-weighted MRI signals at their rims) are more common in progressive MS than in RRMS. • Persistent focal leptomeningeal inflammation, detectable with gadolinium contrastenhanced T2 fluid attenuation inversion recovery MRI in many people with MS (particularly progressive MS), is associated with cortical lesions and accelerated cortical atrophy. • Translocator protein (TSPO) PET can detect increased innate immune activation in brains of people with MS with typically greater activation in secondary progressive MS than in relapsing-remitting MS. Indirect evidence suggests that magnetic resonance spectroscopy measures of myo-inositol and some more recently introduced PET measures both can reflect contributions of astrocyte activation to brain innate immune responses.

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The Role of Immunosenescence in Neurodegenerative Diseases

Cited by 97 publications

References 124 publications

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?

Chronic inflammation in multiple sclerosis — seeing what was always there

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