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Neuronal and non-neuronal cell types

Discover novel multiplex panels for Neurobiology Research

Invitrogen ProcartaPlex Neurobiology Immunoassay Kits allow simultaneous quantitation of up to 18 soluble biomarker molecules for humans, to provide a more complete profile of neurodegeneration, neuroinflammation, brain injury and other trophic factors. By simultaneous measurement of key biomarker proteins in a single sample, ProcartaPlex Neurobiology Immunoassays reduce the variances that could occur when testing each sample in multiple single assays. Use preconfigured panels or select from single targets to create your own custom panel to study these human biomarkers.

 
 
 

Neuroinflammation and neurodegeneration research

The central nervous system (CNS), consisting of the brain and spinal cord, is protected from external influences by the blood-brain barrier (BBB). The term neuroinflammation has been used to describe the different inflammatory processes occurring in the CNS, involving both the innate and adaptive immune system, in response to pathological conditions and diseases. While neuroinflammation is triggered in response to perturbed CNS homeostasis, it has been shown to contribute to both normal brain development and neuropathological events in the CNS.

A variety of conditions or diseases of the CNS including brain trauma, stroke, multiple sclerosis, Parkinson’s disease (PD) or Alzheimer’s disease (AD) can trigger neuroinflammation and dysfunction of the BBB. Acting in concert with ageing, (epi-)genetics, the environment and other risk factors can strongly influence the onset and progression of these diseases. For example, traumatic brain injury has been established as a risk factor for the development of neurodegenerative diseases and dementia at later stages of life. In response to insults that perturb homeostasis in the CNS, a rapid and early activation of the glial cells form the acute inflammatory response. This leads to the repair of the damaged area but if the challenge is not cleared and persists, the activation of the response is exaggerated, becomes chronic and can result in tissue degeneration and even the drastic loss of blood-brain barrier integrity.

Origins of biomarkers for neuroinflammation, traumatic brain injury and neurodegeneration
 

Figure 1. Major neuronal and non-neuronal cell types of the CNS and candidate biomarkers for neuroinflammation, brain injury and neurodegeneration. This schematic depicts possible origins of biomarkers for neuroinflammation, traumatic brain injury and neurodegeneration. Abbreviations: GFAP (glial fibrillary acidic protein); S100B (S100 calcium-binding protein B); NCAM-1 (neural cell adhesion molecule -1); NF-H (neurofilament heavy polypeptide); UCHL1 (ubiquitin carboxyl-terminal hydrolase isoenzyme L1); TREM-2 (triggering receptor expressed on myeloid cells 2); CHI3L1/YKL-40 (chitinase-3-like protein 1/protein with first three N-terminal amino acids, tyrosine(Y), lysine(K), and leucine(L) with apparent molecular weight of 40); sRAGE (soluble receptor for advanced glycation end products); NGF-beta (nerve growth factor – beta); BDNF (brain-derived neurotrophic factor); GDNF (glial cell-derived neurotrophic factor); CTNF (ciliary neurotrophic factor); BACE1 (beta-secretase 1); KLK6 (kallikrein related peptidase 6); TDP-43 (TAR DNA-binding protein – 43).

 

The disruption of the blood-brain barrier may result in an increase in the concentrations of brain-specific molecules in circulation. Therefore, the quantification of these molecules in accessible biofluids such as cerebrospinal fluid (CSF) or blood may help to identify promising candidate biomarkers for tracking both the acute and chronic phases of the inflammatory response and to better understand the progression of neurodegenerative diseases. Antibody-based techniques such as immunoassays can be used to elucidate whether these biomarkers truly exhibit a patient-independent behavior across the population in acute and chronic phases and may serve as surrogate for other more expensive methods. As these biomarkers may show distinct kinetics/kinetic profiles, the ability to measure and track more than one biomarker over time opens up the avenue of a deeper and more thorough understanding of the progression of neuroinflammation and neurodegenerative diseases. Multiplexed immunoassays offer one such possibility, for example, allowing for the simultaneous measurement of factors indicative of brain injury including those released due to astroglial injury (GFAP, S100B) axonal injury (NF-H) and neuronal cell body injury (UCH-L1) (ProcartaPlex Cat. No. EPX040-15827-901).

Multiplexed immunoassays panels provide a powerful biomarker detection tool to help distinguish diseased from non-diseased states and/or even differentiate between neurodegenerative diseases. The presence of high levels of both tau and phospho-tau in CSF in combination with low levels of β-amyloid (1-42) has been established as pathophysiological marker profile to define AD by the 2014 International Working Group -2 (IWG-2) for New Research Criteria for the Diagnosis of AD (ProcartaPlex Cat. No. EPX180-15837-901). Recent work has shown that the ratio of Aβ 1-42 to Aβ 1-40 may work as a better biomarker to distinguish AD dementia from non-AD dementias when compared to determination of Aβ 1-42 levels alone. The ProcartaPlex Neurodegeneration Panel 1 (Cat. No. EPX090-15836-901) allows for the simultaneous measurement of both Aβ 1-42 and Aβ 1-40 in addition to other biomarkers such as Neurogranin, NCAM and TDP-43. These proteins have also been shown to play a role in the pathologies of diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FLTD-U) and therefore may be promising candidate biomarkers for these diseases.

Levels of 18 biomarkers from ungrouped human adult and pediatric patient cerebrospinal fluid samples tested using the ProcartaPlex plex Human Neuroscience Panel.

Figure 2A.

Levels of 18 biomarkers from ungrouped human adult and pediatric patient cerebrospinal fluid samples with metastatic brain cancer tested using the ProcartaPlex plex Human Neuroscience Panel

Figure 2B.
 Click images to enlarge

Figure 2: Quantification of biomarkers in cerebrospinal fluid and plasma. A) Levels of 18 biomarkers from 10 ungrouped human adult and 10 human pediatric patient cerebrospinal fluid samples were tested using the ProcartaPlex 18plex Human Neuroscience Panel (Cat. No. EPX180-15837-901). Results of the ungrouped human samples are shown for all targets. B) Levels of 18 biomarkers from 10 ungrouped human adult patients with metastatic brain cancer and 10 human adult control patient plasma (EDTA) samples were tested using the ProcartaPlex 18plex Human Neuroscience Panel (Cat. No. EPX180-15837-901). Results of the ungrouped human samples are shown for all targets. [Data provided by The Washington University Bursky Center for Human Immunology and Immunotherapy Programs (CHiiPs) Immunomonitoring Laboratory]

 
 
 

The relationship between neurotrophic factors (NTFs) and glia (microglia, astrocytes) is crucial for both the developing and adult brain as they play a key role in the development of neurons, their plasticity, their protection and repair. While age has been shown to impact basal levels, expression patterns of some of these neurotrophic factors suggest they may be upregulated post injury. NTFs provide potent trophic support to neurons to elicit pro-survival and pro-functional responses, thus making them viable drug candidates for treatment for a multitude of neurodegenerative disorders. The ProcartaPlex Neurotrophic Factor panel (Cat. No. EPX040-15828-901) allows for the simultaneous investigation of several key NTFs, including BDNF, NGF, CTNF and GDNF.

In addition to NTFs, cytokines and chemokines are also involved in CNS tissue homeostasis and neuroinflammation. These are primarily produced by CNS-resident cells such as astrocytes and microglia in CNS proteopathies or by CNS-invading blood-borne leukocytes in neuroinflammatory diseases. Cytokine, chemokine and growth factor profiling (ProcartaPlex Cat. No. EPXR450-12171-901) might provide additional insights into underlying neuropathological processes to improve the ability to drive advances in biomarker-guided therapeutic approaches for neuroinflammatory and neurodegenerative disorders.

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