Inflammation in mild cognitive impairment due to Parkinson's disease, Lewy body disease, and Alzheimer's disease

King, Eleanor M.; O’Brien, John; Donaghy, Paul C.; Williams‐Gray, Caroline H.; Lawson, Rachael A.; Morris, Christopher M.; Barnett, Nicola; Olsen, Kirsty; Martin-Ruiz, Carmen; Burn, David J.; Yarnall, Alison J.; Taylor, John‐Paul; Duncan, Gordan W.; Khoo, Tien K.; Thomas, Alan

doi:10.1002/gps.5124

Cited by 38 publications

(29 citation statements)

References 30 publications

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“…In line with this, inflammatory biomarkers were recently examined in studies of Rapid Eye Movement (REM) Behavior Disorder (RBD) patients. 75,76 There is some circumstantial evidence from studies of blood cytokines, which suggest that these are higher in early disease and decline with time, 77 as well as some evidence that blood lymphocytes recognizing α-synuclein antigens can be detected early. Stokholm et al 78 have observed increased PK 11195 binding in subjects with RBD.…”

Section: Question 8: When Does Inflammation Begin In Pd?mentioning

confidence: 99%

Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease

2020

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Parkinson's disease is a progressive and debilitating disorder that has so far eluded attempts to develop disease‐modifying treatment. Both epidemiological and genetic studies support a role of neuroinflammation in the pathophysiology of Parkinson's disease. Postmortem studies and experimental analyses suggest the involvement of both innate and adaptive immunity in the degenerative process. There is also some circumstantial evidence for effects of immune therapies on the disease. In the present article, we review 10 unanswered questions related to neuroinflammatory processes in Parkinson's disease with the goal of stimulating research in the field and accelerating the clinical development of neuroprotective therapies based on anti‐inflammatory strategies. © 2020 International Parkinson and Movement Disorder Society

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Section: Question 8: When Does Inflammation Begin In Pd?mentioning

confidence: 99%

Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease

2020

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“…Serum high sensitivity Creactive protein (hsCRP) was assayed on the Siemens Advia 2400 Chemistry analyser (Siemens Healthcare Diagnostics, Frimley, UK) 44 . Serum cytokines were measured using Meso Scale Discovery (MSD) V-PLEX sandwich immunoassays 45,46 , and plates read on an MSD QuickPlex SQ 120, as in a previous study conducted in our laboratory 47,48 . MSD Pro-inflammatory Panel 1 (human) kit was used for the measurement of IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α, and a custom Cytokine Panel 1 (human) kit was used for the measurement of IL-7, IL-17 A and vascular endothelial growth factor VEGF-A.…”

Section: Biomarkers Of Peripheral Inflammationmentioning

confidence: 99%

PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers

et al. 2020

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Depression is associated with peripheral inflammation, but its link with brain microglial activity remains unclear. In seven healthy males, we used repeated translocator protein-Positron Emission Tomography (TSPO-PET) dynamic scans with [ 11 C]PBR28 to image brain microglial activation before and 24 h after the immune challenge interferon (IFN)-α. We also investigated the association between changes in peripheral inflammation, changes in microglial activity, and changes in mood. IFN-α administration decreased [ 11 C]PBR28 PET tissue volume of distribution (Vt) across the brain (−20 ± 4%; t 6 = 4.1, p = 0.01), but after correction for radioligand free-plasma fraction there were no longer any changes (+23 ± 31%; t = 0.1, p = 0.91). IFN-α increased serum IL-6 (1826 ± 513%, t 6 = −7.5, p < 0.001), IL-7 (39 ± 12%, t 6 = −3.6, p = 0.01), IL-10 (328 ± 48%, t 6 = −12.8, p < 0.001), and IFN-γ (272 ± 64%, t 6 = −7.0, p < 0.001) at 4-6 h, and increased serum TNF-α (49 ± 7.6%, t 6 = −7.5, p < 0.001), IL-8 (39 ± 12%, t 6 = −3.5, p = 0.013), and C-reactive protein (1320 ± 459%, t 6 = −7.2, p < 0.001) at 24 h. IFN-α induced temporary mood changes and sickness symptoms after 4-6 h, measured as an increase in POMS-2 total mood score, confusion and fatigue, and a decrease in vigor and friendliness (all p ≤ 0.04). No association was found between changes in peripheral inflammation and changes in PET or mood measures. Our work suggests that brain TSPO-PET signal is highly dependent of inflammation-induced changes in ligand binding to plasma proteins. This limits its usefulness as a sensitive marker of neuroinflammation and consequently, data interpretation. Thus, our results can be interpreted as showing either that [ 11 C]PBR28 is not sensitive enough under these conditions, or that there is simply no microglial activation in this model.

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“…In ammation plays a vital role in neurodegenerative diseases [51,59], such as Alzheimer's disease [60], dementia with Lewy bodies [61], Wilson's disease [62], Parkinson's disease [63], multiple sclerosis [64]. Serum CHE activities is closely related to the in ammation and is involved in many pathophysiological processes of nervous system diseases [65].…”

Section: Discussionmentioning

confidence: 99%

Reduced Serum Cholinesterase Activity Distinguishes Hepatic Encephalopathy From 48 Types of Human Diseases

Rong¹,

Zhang²,

Zhang³

et al. 2020

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Background: Hepatic encephalopathy is a complication of central nervous systems due to liver failure-related brain inflammation. Less than half of patients suffering from liver failure develop hepatic encephalopathy, which suggests other factors beyond liver failure might contribute to hepatic encephalopathy. Indeed, we reported previously that the levels of serum direct bilirubin, a liver cell-made product, are counter-intuitively highest in hepatic encephalopathy patients among 72 clinically defined diseases. In current study, we tested if cholinesterase could serve as a biomarker for hepatic encephalopathy by comparing serum cholinesterase activities among 48 different types of human diseases.Methods: The activity of serum cholinesterase was determined by the standard “continuous monitoring method” in the clinical laboratory of the hospital where the serum cholinesterase activities from 137,305 independent tests with 48 clinically defined diseases and 3,387 independent tests from healthy individuals who came to the hospital for physical examination during the past 5 years were retrieved. All data were analyzed with RStudio V.1.3.1073 and python libraries 3.8.Results: We found that all 48 types of diseases had decreased cholinesterase activity compared to control based on either mean or median values. Remarkably, hepatic encephalopathy had the lowest cholinesterase activity and the serum cholinesterase activity was the best biomarker for hepatic encephalopathy (AUC 0.99, sensitivity 100%, and specificity 99%) among all diseases. Moreover, two component analysis of cholinesterase activity distributions revealed hepatic encephalopathy resembled preeclampsia and uremia whereas cirrhosis resembled multiple myeloma, leukemia, myeloproliferative disorder, and liver cancer.Conclusions: Decreased cholinesterase activity was an almost perfect serum biomarker for patients suffering hepatic encephalopathy at all stages. The resemblance of hepatic encephalopathy to preeclampsia and uremia based on cholinesterase activities provided new insight in understanding hepatic encephalopathy etiology beyond liver failure.

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Inflammation in mild cognitive impairment due to Parkinson's disease, Lewy body disease, and Alzheimer's disease

Cited by 38 publications

References 30 publications

Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease

Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease

PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers

Reduced Serum Cholinesterase Activity Distinguishes Hepatic Encephalopathy From 48 Types of Human Diseases

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