Correlation of Peripheral Immunity With Rapid Amyotrophic Lateral Sclerosis Progression

Murdock, Benjamin J.; Zhou, Tingting; Kashlan, Samy R.; Little, Roderick J. A.; Goutman, Stephen A.; Feldman, Eva L.

doi:10.1001/jamaneurol.2017.2255

Cited by 147 publications

(177 citation statements)

References 55 publications

Supporting

Mentioning

156

Contrasting

Order By: Relevance

“…Studies directed at mapping peripheral adaptive immune profiles in ALS and associating immune alterations to clinical disease phenotypes have been conducted . For example, ALS patients were shown to have altered levels of CD4+, CD8+, and natural killer T cells in the peripheral blood compared to healthy controls, and such alterations were shown to be associated with the progression rate of the disease .…”

Section: Discussionmentioning

confidence: 99%

“…Studies directed at mapping peripheral adaptive immune profiles in ALS and associating immune alterations to clinical disease phenotypes have been conducted. [30][31][32] For example, ALS patients were shown to have altered levels of CD4+, CD8+, and natural killer T cells in the peripheral blood compared to healthy controls, and such alterations were shown to be associated with the progression rate of the disease. 30,31,33 The present study did not, however, reveal different associations of specific cell types with the risk of ALS or different concentrations of specific cell types between ALS patients and individuals without ALS during the 20 years before ALS diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…[30][31][32] For example, ALS patients were shown to have altered levels of CD4+, CD8+, and natural killer T cells in the peripheral blood compared to healthy controls, and such alterations were shown to be associated with the progression rate of the disease. 30,31,33 The present study did not, however, reveal different associations of specific cell types with the risk of ALS or different concentrations of specific cell types between ALS patients and individuals without ALS during the 20 years before ALS diagnosis. The fact that previous studies compared leukocyte concentrations among clinical patients with ALS to healthy volunteers, whereas the present study examined leukocyte concentrations long before diagnosis of ALS patients to randomly selected population controls, might have contributed to part of the contrasting results pattern.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow‐up

Yazdani

Mariosa

Hammar

et al. 2019

Annals of Neurology

View full text Add to dashboard Cite

Objective To assess the associations of several blood immune biomarkers with the future risks of amyotrophic lateral sclerosis and Parkinson disease in a prospective cohort study with 20 years of follow‐up. Methods The Swedish Apolipoprotein‐Related Mortality Risk study is a longitudinal cohort study including 812,073 participants with repeated blood biomarker measurements between 1985 and 1996 and a follow‐up until 2011. Using a Cox model, we first estimated hazard ratios of amyotrophic lateral sclerosis and Parkinson disease in relation to leukocytes, immunoglobulin G, haptoglobin, and uric acid. We further described the temporal changes of these biomarkers during the 20 years prior to the diagnosis of these diseases. Results A total of 585 incident cases of amyotrophic lateral sclerosis and 3,769 incident cases of Parkinson disease were identified during the follow‐up. Increasing concentrations of leukocytes, haptoglobin, and uric acid were associated with a lower risk of Parkinson disease. No statistically significant association was, however, noted between the studied biomarkers and amyotrophic lateral sclerosis. Parkinson disease patients appeared to have lower levels of leukocytes and haptoglobin between 20 and 10 years before diagnosis and lower levels of uric acid during the 20 years before diagnosis, compared to controls, although statistically significant differences were only noted during parts of the respective time intervals after multivariable adjustment. No clear differences were noted between patients with amyotrophic lateral sclerosis and controls. Interpretation If verified in studies of independent populations, our findings may suggest a different role of systemic inflammation on the risk of Parkinson disease compared to amyotrophic lateral sclerosis. ANN NEUROL 2019;86:913–926

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow‐up

Yazdani

Mariosa

Hammar

et al. 2019

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…Rather, glial responses to motor neuron degeneration may determine disease severity. Indeed, several studies in humans seeking factors contributing to disease progression have found an increased presence of pro‐inflammatory markers in CSF and blood of patients with rapidly progressive ALS. Moreover, a recent data‐driven approach evaluating the ALS transcriptome, neuropathology and genome wide associations, underscored the link between microglia activation and disease progression in ALS .…”

Section: Discussionmentioning

confidence: 99%

Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes

Gorter

Stephenson

Nutma

et al. 2018

Neuropathology Appl Neurobio

View full text Add to dashboard Cite

Aims Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2–5 years of onset. Neuroinflammation is a hallmark of ALS pathology characterized by activation of glial cells, which respond by upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated the association between ALS disease duration, lower motor neuron loss, TARDNA‐binding protein 43 (TDP‐43) pathology, neuroinflammation and HSPB expression. Methods With immunohistochemistry, we examined HSPB1, HSPB5, HSPB6, HSPB8 and HSP16.2 expression in cervical, thoracic and sacral spinal cord regions in 12 ALS cases, seven with short disease duration (SDD), five with moderate disease duration (MDD), and ten age‐matched controls. Expression was quantified using ImageJ to examine HSP expression, motor neuron numbers, microglial and astrocyte density and phosphorylated TDP‐43 (pTDP‐43+) inclusions. Results SDD was associated with elevated HSPB5 and 8 expression in lateral tract astrocytes, while HSP16.2 expression was increased in astrocytes in MDD cases. SDD cases had higher numbers of motor neurons and microglial activation than MDD cases, but similar levels of motor neurons with pTDP‐43+ inclusions. Conclusions Increased expression of several HSPBs in lateral column astrocytes suggests that astrocytes play a role in the pathogenesis of ALS. SDD is associated with increased microgliosis, HSPB5 and 8 expression in astrocytes, and only minor changes in motor neuron loss. This suggests that the interaction between motor neurons, microglia and astrocytes determines neuronal fate and functional decline in ALS.

show abstract

“…Along this line, ALS patients display higher levels of circulating monocytes, neutrophils, and CD4 lymphocytes, with the increased number positively correlating with a more rapid progression of the disease [132, 138]. Mouse models as well as ALS patients also have high levels of cytotoxic CD8 lymphocytes and circulating natural killer cells [133, 139, 140].…”

Section: Neuroinflammation In Neurodegenerative Diseasesmentioning

confidence: 99%

Neuroimmune and Inflammatory Signals in Complex Disorders of the Central Nervous System

Liberman

Trías

Chagas

et al. 2018

Neuroimmunomodulation

View full text Add to dashboard Cite

An extensive microglial-astrocyte-monocyte-neuronal cross talk seems to be crucial for normal brain function, development, and recovery. However, under certain conditions neuroinflammatory interactions between brain cells and neuroimmune cells influence disease outcome and brain pathology. Microglial cells express a range of functional states with dynamically pleomorphic profiles from a surveilling status of synaptic transmission to an active player in major events of development such as synaptic elimination, regeneration, and repair. Also, inflammation mediates a series of neurotoxic roles in neuropsychiatric conditions and neurodegenerative diseases. The present review discusses data on the involvement of neuroinflammatory conditions that alter neuroimmune interactions in four different pathologies. In the first section of this review, we discuss the ability of the early developing brain to respond to a focal lesion with a rapid compensatory plasticity of intact axons and the role of microglial activation and proinflammatory cytokines in brain repair. In the second section, we present data of neuroinflammation and neurodegenerative disorders and discuss the role of reactive astrocytes in motor neuron toxicity and the progression of amyotrophic lateral sclerosis. In the third section, we discuss major depressive disorders as the consequence of dysfunctional interactions between neural and immune signals that result in increased peripheral immune responses and increase proinflammatory cytokines. In the last section, we discuss autism spectrum disorders and altered brain circuitries that emerge from abnormal long-term responses of innate inflammatory cytokines and microglial phenotypic dysfunctions.

show abstract

Correlation of Peripheral Immunity With Rapid Amyotrophic Lateral Sclerosis Progression

Cited by 147 publications

References 55 publications

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow‐up

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow‐up

Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes

Neuroimmune and Inflammatory Signals in Complex Disorders of the Central Nervous System

Contact Info

Product

Resources

About