scholarly journals Neuropathologic underpinnings of PET and fluid biomarker measures

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Melissa E. Murray
Keyword(s):  
Fluid Biomarker

scholarly journals Toll-like receptor linked cytokine profiles in cerebrospinal fluid discriminate neurological infection from sterile inflammation

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Simone M Cuff ◽  
Joseph P Merola ◽  
Jason P Twohig ◽  
Matthias Eberl ◽  
William P Gray
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Practice ◽  
Inflammatory Response ◽  
Nosocomial Infection ◽  
Pathway Analysis ◽  
Interleukin 6 ◽  
Sterile Inflammation ◽  
Interleukin 17 ◽  
Toll Like Receptor ◽  
Fluid Biomarker

Abstract Rapid determination of an infective aetiology causing neurological inflammation in the cerebrospinal fluid can be challenging in clinical practice. Post-surgical nosocomial infection is difficult to diagnose accurately, as it occurs on a background of altered cerebrospinal fluid composition due to the underlying pathologies and surgical procedures involved. There is additional diagnostic difficulty after external ventricular drain or ventriculoperitoneal shunt surgery, as infection is often caused by pathogens growing as biofilms, which may fail to elicit a significant inflammatory response and are challenging to identify by microbiological culture. Despite much research effort, a single sensitive and specific cerebrospinal fluid biomarker has yet to be defined which reliably distinguishes infective from non-infective inflammation. As a result, many patients with suspected infection are treated empirically with broad-spectrum antibiotics in the absence of definitive diagnostic criteria. To begin to address these issues, we examined cerebrospinal fluid taken at the point of clinical equipoise to diagnose cerebrospinal fluid infection in 14 consecutive neurosurgical patients showing signs of inflammatory complications. Using the guidelines of the Infectious Diseases Society of America, six cases were subsequently characterized as infected and eight as sterile inflammation. Twenty-four contemporaneous patients with idiopathic intracranial hypertension or normal pressure hydrocephalus were included as non-inflamed controls. We measured 182 immune and neurological biomarkers in each sample and used pathway analysis to elucidate the biological underpinnings of any biomarker changes. Increased levels of the inflammatory cytokine interleukin-6 and interleukin-6-related mediators such as oncostatin M were excellent indicators of inflammation. However, interleukin-6 levels alone could not distinguish between bacterially infected and uninfected patients. Within the patient cohort with neurological inflammation, a pattern of raised interleukin-17, interleukin-12p40/p70 and interleukin-23 levels delineated nosocomial bacteriological infection from background neuroinflammation. Pathway analysis showed that the observed immune signatures could be explained through a common generic inflammatory response marked by interleukin-6 in both nosocomial and non-infectious inflammation, overlaid with a toll-like receptor-associated and bacterial peptidoglycan-triggered interleukin-17 pathway response that occurred exclusively during infection. This is the first demonstration of a pathway dependent cerebrospinal fluid biomarker differentiation distinguishing nosocomial infection from background neuroinflammation. It is especially relevant to the commonly encountered pathologies in clinical practice, such as subarachnoid haemorrhage and post-cranial neurosurgery. While requiring confirmation in a larger cohort, the current data indicate the potential utility of cerebrospinal fluid biomarker strategies to identify differential initiation of a common downstream interleukin-6 pathway to diagnose nosocomial infection in this challenging clinical cohort.

O2-07-03: Validating predicted biological effects of Alzheimer's disease associated SNPs using cerebrospinal fluid biomarker levels

2010 ◽  
Vol 6 ◽  
pp. S112-S113 ◽  
Author(s):  
John S.K. Kauwe ◽  
Carlos Cruchaga ◽  
Sarah Bertelsen ◽  
Kevin Mayo ◽  
Wayne Latu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Biological Effects ◽  
Fluid Biomarker

Clusterin, a New Cerebrospinal Fluid Biomarker in Severe Subarachnoid Hemorrhage: A Pilot Study

2017 ◽  
Vol 107 ◽  
pp. 424-428 ◽  
Author(s):  
Norbert Wąsik ◽  
Bartosz Sokół ◽  
Marcin Hołysz ◽  
Witold Mańko ◽  
Robert Juszkat ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Pilot Study ◽  
Fluid Biomarker

Kynurenine Is a Cerebrospinal Fluid Biomarker for Bacterial and Viral Central Nervous System Infections

2019 ◽  
Vol 220 (1) ◽  
pp. 127-138 ◽  
Author(s):  
Kurt-Wolfram Sühs ◽  
Natalia Novoselova ◽  
Maike Kuhn ◽  
Lena Seegers ◽  
Volkhard Kaever ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Central Nervous System Infections ◽  
Fluid Biomarker

scholarly journals An Alternative Macrophage Activation Pathway Regulator, CHIT1, May Provide a Serum and Synovial Fluid Biomarker of Periprosthetic Osteolysis

2017 ◽  
Vol 14 (2) ◽  
pp. 148-152 ◽  
Author(s):  
Samir K. Trehan ◽  
Lester Zambrana ◽  
Jonathan E. Jo ◽  
Ed Purdue ◽  
Athanos Karamitros ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Macrophage Activation ◽  
Periprosthetic Osteolysis ◽  
Activation Pathway ◽  
Fluid Biomarker

scholarly journals The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity

2016 ◽  
Vol 113 (32) ◽  
pp. E4708-E4715 ◽  
Author(s):  
Timothy S. Jarvela ◽  
Hoa A. Lam ◽  
Michael Helwig ◽  
Nikolai Lorenzen ◽  
Daniel E. Otzen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Primary Cultures ◽  
Lewy Bodies ◽  
Vitro Assay ◽  
Amino Terminal ◽  
Neuroprotective Function ◽  
Fluid Biomarker

Emerging evidence strongly suggests that chaperone proteins are cytoprotective in neurodegenerative proteinopathies involving protein aggregation; for example, in the accumulation of aggregated α-synuclein into the Lewy bodies present in Parkinson’s disease. Of the various chaperones known to be associated with neurodegenerative disease, the small secretory chaperone known as proSAAS (named after four residues in the amino terminal region) has many attractive properties. We show here that proSAAS, widely expressed in neurons throughout the brain, is associated with aggregated synuclein deposits in the substantia nigra of patients with Parkinson’s disease. Recombinant proSAAS potently inhibits the fibrillation of α-synuclein in an in vitro assay; residues 158–180, containing a largely conserved element, are critical to this bioactivity. ProSAAS also exhibits a neuroprotective function; proSAAS-encoding lentivirus blocks α-synuclein-induced cytotoxicity in primary cultures of nigral dopaminergic neurons, and recombinant proSAAS blocks α-synuclein–induced cytotoxicity in SH-SY5Y cells. Four independent proteomics studies have previously identified proSAAS as a potential cerebrospinal fluid biomarker in various neurodegenerative diseases. Coupled with prior work showing that proSAAS blocks β-amyloid aggregation into fibrils, this study supports the idea that neuronal proSAAS plays an important role in proteostatic processes. ProSAAS thus represents a possible therapeutic target in neurodegenerative disease.

scholarly journals Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker–based case–control study

PLoS Medicine ◽  
2020 ◽  
Vol 17 (8) ◽  
pp. e1003289 ◽  
Author(s):  
Hana Saddiki ◽  
Aurore Fayosse ◽  
Emmanuel Cognat ◽  
Séverine Sabia ◽  
Sebastiaan Engelborghs ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Apolipoprotein E ◽  
Case Control Study ◽  
Case Control ◽  
Fluid Biomarker ◽  
Control Study ◽  
Apolipoprotein E Genotype
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