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Biomarkers for Neuroscience Research

Discover Biomarkers

Understanding and treating neurological diseases is a major challenge due to the complexity and dynamic environment of the central nervous system (CNS). Fortunately, with the use of neuroscience biomarkers these complexities start to unfold and come to life. Biomarkers are essential indicators of neurological disease states and contribute to the understanding of pathogenic molecular mechanisms by revealing affected pathways and processes. Count on our comprehensive portfolio of highly validated immunoassays and instrumentation so you can select the appropriate tools and effectively discover, detect, and monitor your neuroscience biomarkers. Ultimately, with the use of sensitive and specific biomarkers, derived from different platforms, neuroscientists can unearth new neurological findings and forge a path for new therapeutic discoveries.

Biomarker studies have different research needs. Here we highlight leading methods that address key areas for success:

RobustSensitiveVisual

Use this guide to DISCOVER more about each platform and how it fits your purpose.

 

ROBUST

Various research labs measure and evaluate neurological biomarkersAs various research labs measure and evaluate neurological biomarkers, highly validated assays are essential to ensure accuracy, precision and reproducibility. This level of robustness allows you to produce results you can trust, with minimal repetition.

CHALLENGE

Inconsistent batches make it difficult to quantify biomarkers.

> SOLUTION

 As your research uncovers the significant role of biomarkers in neurological disease states, you need a reliable partner for quality assays and consistent performance. Validate and quantify your biomarkers with our ELISA and MILLIPLEX® MAP (multi-analyte profiling) assays that provide reproducibility in every lot, backed by unwavering technical support. Be assured whether you are quantifying basic research or critical patient targets, you can rely on our assays to provide consistent results.

Enzyme-Linked Immunosorbent Assays (ELISA)

 Get a fuller picture of the complexities associated with non-disease and disease states of the nervous system with reliable quantification of biomarkers in sera and lysates using trusted ELISA techniques. ELISAs combine the specificity of antibodies with the sensitivity of simple enzyme assays, so you can successfully quantify critical targets. We lead in developing neuro-specific ELISAs, with over 20 ELISAs supporting neuroscience research and more than 1,000 available within our comprehensive ELISA portfolio.

 

Highlighted Neuroscience ELISAs

 

Description Species Standard Curve Range Sensitivity Sample Volume Cat. No.
α-Synuclein Human, Mouse, Rat 3–60 ng/mL 3 ng/mL 100 μL NS400
Amyloid beta 1–40 Human 16–500 pg/mL 4 pg/mL 50 μL EZHS40
Amyloid beta 1–42 Human 16–500 pg/mL 5 pg/mL 50 μL EZHS42
Amyloid beta, Set Human Contains 1 each of EZHS40 and EZHS42 EZHS-SET
Amyloid beta (Brain) 1–40 Human 16–500 pg/mL 4 pg/mL 50 μL EZBRAIN40
Amyloid beta (Brain) 1–42 Human 16–500 pg/mL 5 pg/mL 50 μL EZBRAIN42
Amyloid beta (Brain), Set Human Contains 1 each of EZBRAIN40 and EZBRAIN42 EZBRAIN-SET
BDNF (Brain-Derived Neurotrophic Factor) Human, Rat 7.8–500 pg/mL 7.8 pg/mL 50 μL CYT306
GFAP (Glial Fibrillary Acidic Protein) Human, Mouse, Rat 1.5–100 ng/mL 1.5 ng/mL 100 μL NS830
NGF (Nerve Growth Factor) Mouse, Rat 10–1000 pg/mL 10–15 pg/mL 50 μL CYT304
NPY (Neuropeptide Y) Human 5–1000 pg/mL 2 pg/mL 50 μL EZHNPY-25K
NPY (Neuropeptide Y) Mouse, Rat 0.01–2 ng/mL 0.004 ng/mL 20 μL EZRMNPY-27K
PEDF (Pigment Epithelium-Derived Factor) Human 0.9–62.5 ng/mL 0.9 ng/mL 50 μL CYT420
Phosphorylated Neurofilament, (pNF-H) Sandwich Multi-Species 0.0293–15 ng/mL 0.0585 ng/mL 1–10 μL NS170
S100B Human 2.7–2000 pg/mL 1.3 pg/mL 50 μL EZHS100B-33K

Discover our comprehensive portfolio of ELISAs at SigmaAldrich.com/Neuro-ELISA

 

Explore Application References
Plog, BA et al. Biomarkers of Traumatic Injury Are Transported from Brain to Blood via the Glymphatic System. J. Neurosci. 2015;35(2): 518-526. Mothapo, KM et al. Amyloidbeta-42 (Aβ-42), neprilysin and cytokine levels. A pilot study in patients with HIV related cognitive impairments. J Neuroimmunol. 2015;282:73-79.
Lagerstedt, L et al. H-FABP: A new biomarker to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury. PLoS ONE. 2017;12(4):e0175572. Deng, H et al. Elevated Plasma S100B, Psychotic Symptoms, and Cognition in Schizophrenia. Psychiatr Q. 2017 Apr 24.

 

CHALLENGE
Low volume samples can create serious challenges for analyzing data.

> SOLUTION

Multiplexed Immunoassays (MILLIPLEX® MAP Assays)

Neuroscientists are often limited by their sample amount (e.g. cerebrospinal fluid, plasma, etc.) and need a method that allows for reproducibility with low volume sample requirements. Count on our neuroscience-specific MILLIPLEX® MAP panels, where you can simultaneously measure multiple biomarker analytes in a single sample, in a single plate well. This multiplex method can save you time and valuable sample material so you can bring your neuroscience biomarkers to life.

MILLIPLEX® MAP multiplex assays enable you to measure neuroscience-related biomarkers. A sample of key targets are shown below:

 

Neurodegenerative Disease
Amyloid β40 Amyloid β42 Apo E GDNF sICAM-1
PAI-1 sRAGE S100B sVCAM-1  
Neurological Disorders
AGP CP NGFβ NSE Park5
Park7 Phospho Tau SAP Tau  
Neuropeptide/Neurohormone Signaling
α-MSH Cortisol Melatonin Orexin A Oxytocin
Substance P        

s = Soluble
 

Highlighted MILLIPLEX® MAP Neuroscience Panels

Human Amyloid Beta and Tau (CSF samples)
(Cat. No. HNABTMAG-68K)

Amyloid beta 1-40
Amyloid beta 1-42
pTau (Thr181)
Tau (total)

Human Neuroscience Panel 1 (CSF samples)
(Cat. No. HNS1MAG-95K)

α-Synuclein
Glial Fibrillary Acidic
Protein (GFAP)
Neuron-specific
Enolase (NSE)
PARK5/UCHL1
PARK7/DJ1
Transglutaminase 2
(TGM2)

Human Neurodegenerative Disease Panel 1
(Cat. No. HNDG1MAG-36K)

α-2-Macroglobulin
Apo AI
Apo CIII
Apo E
Complement C3
Complement Factor H

Human Neurodegenerative Disease Panel 2
(Cat. No. HNDG2MAG-36K)

α-1-Antitrypsin (A1AT)
C4
CRP
MIP-4/PARC/CCL18
PEDF
Serum Amyloid P
(SAP)

Human Neurodegenerative Disease Panel 3
(Cat. No. HNDG3MAG-36K)

BDNF
Cathepsin D
sICAM-1
Myeloperoxidase
(MPO)
sNCAM
PAI-1 (total)
PDGF-AA
PDGF-AB/BB
RANTES/CCL5
sVCAM-1

Human Neurodegenerative
Disease Panel 4
(CSF samples)

(Cat. No. HNDG4MAG-36K)

Amyloid beta 1-40
Amyloid beta 1-42
GDNF
sRAGE
S100B

Human Neurological
Disorders Panel 3

(Cat. No. HND3MAG-39K)

Angiotensinogen
(AGT)
Contactin-1
Fetuin A
Kallikrein-6
Osteopontin (OPN)
Soluble Superoxide
Dismutase 1 (sSOD1)
Soluble Superoxide
Dismutase 2 (sSOD2)

Human Neuropeptide ■ ^
(Cat. No. HNPMAG-35K)

α-MSH
β-Endorphin
Neurotensin
Orexin A
Oxytocin
Substance P

Human Circadian Stress ■ ^
(Cat. No. HNCSMAG-35K)

Cortisol Melatonin

Discover our comprehensive portfolio of multiplexed immunoassays at SigmaAldrich.com/Neuro-Milliplex

 

Protein Detection Platform: Luminex®Protein Detection Platform: Luminex®

Use trusted Luminex® xMAP® technology to enable multivariate analysis of processes that underlie neural development, homeostasis and pathogenesis — all while conserving your precious samples.

MILLIPLEX® MAP Multiplex Detection Using Luminex® xMAP® Technology

  • Simultaneously measure multiple proteins in a single sample
  • Low sample volume (< 25 μL)
  • Large dynamic range (> 3.5 Logs)

 

Explore Application References
Hye, A et al. Plasma proteins predict conversion to dementia from prodromal disease. Alzheimers Dement. 2014;10(6):799-807. Hu, WT et al. CSF complement 3 and factor H are staging biomarkers in Alzheimer’s disease. Acta Neuropathol Commun. 2016;4:14.
Westwood, S et al. The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer’s pathology. Alzheimers Res Ther. 2017;9:31. Martínez-Muriana, A et al. CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves. Sci Rep. 2016;6:25663.
Öhrfelt, A et al. Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer’s Disease. Dement Geriatr Cogn Dis Extra. 2016;6(2):283–294. Marples, B et al. Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer’s Disease (AD). Radiother Oncol. 2016;118(1):43-51.

 

Instruments

APPLICATION SPOTLIGHT

Human Amyloid Beta and Tau Magnetic Bead Panel
(Cat. No. HNABTMAG-68K)

Alzheimer’s disease (AD), a prog-ressive neurodegenerative disorder, afflicts approximately 36 million people worldwide and is the sixth leading cause of death in the U.S. Two key neuropathological features that exemplify AD are extracellular Amyloid β (Aβ) plaques and intra-cellular neurofibrillary tangles, which are composed of the abnormally hyperphosphorylated protein Tau. Unlike ELISAs and other multiplex kits, the MILLIPLEX® MAP Human Amyloid Beta and Tau Panel enables the simultaneous measurement of Aβ1-40, Aβ1-42, total Tau and phospho-Tau (Thr181) in cerebrospinal fluid (CSF) samples, saving time, money and precious sample.

Multiplex measurement of human non-AD and AD CSF samples

Multiplex measurement of human non-AD and AD CSF samples. Non-AD and AD CSFs samples. Non-AD CSF samples (n = 16) and AD CSF samples (n = 16) were analyzed using the MILLIPLEX® MAP Human Amyloid Beta and Tau Magnetic Bead Panel.

SENSITIVE

Biomarker discovery depends on detection. And when the success of your neuroscience research requires finding and quantifying low-level proteins, you need technology and equipment you can rely on to detect your target.

CHALLENGE
Low abundance biomarkers are difficult to detect.

> SOLUTION

Highly Sensitive Single Molecule Counting (SMC™) Technology

Early detection of low level disease biomarkers in your research models and clinical samples can translate to the discovery and development of early therapeutic intervention in patients. Count on our ultra-sensitive SMC™ technology to provide precise measurement of molecules at levels previously undetectable, leading to unprecedented biomarker insight to fuel your discovery of neurological diseases.

  • Quantify previously undetectable analytes
  • Better stratify sample populations
  • Gain insights into novel neurological mechanisms
  • Require fewer data points for critical decision-making
  • Accelerate drug discovery and development

Reduced Background + Increased Signal

SMC™ technology provides maximum immunoassay performance while following a workflow very similar to traditional ELISA technology, as shown below. By combining a unique assay elution step and robust digital counting, SMC™ technology achieves improved signal-to-noise ratios over traditional immunoassay technologies. SMC™ technology provides enhanced quantification at both low and high levels of expression on one complete system.

Highlighted SMC™ Immunoassays
 

Description Cat. No.
NEUROSCIENCE  
Human Aβ-40 (Coming Soon) 03-0145-00
Human Aβ-42 (Coming Soon) 03-0146-00


Highlighted Inflammation Assays

Over 35 ultra-sensitive SMC™ assays to choose from, for use in humans and other species.
 

Description Cat. No.
INFLAMMATION  
Erenna® IL-17A Immunoassay Kit (V2) 03-0103-00
Erenna® IL-17F Immunoassay Kit (V2) 03-0102-00
Erenna® Human IL-23 Immunoassay Kit 03-0112-00
Erenna® Human IL-6 Immunoassay Kit 03-0089-01
Erenna® Human IL-4 Immunoassay Kit 03-0052-00


Discover our comprehensive portfolio of SMC™ immunoassays

Discover our comprehensive portfolio of SMC™ immunoassays at SigmaAldrich.com/Neuro-SMC

 

Explore Application References  
Wild, EJ et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients. J Clin Invest.2015;125(5):1979-1986. Yang, T et al. A highly sensitive novel immunoassay specifically detects low levels of soluble Aβ oligomers in human cerebrospinal fluid. Alzheimers Res Ther. 2015;7(1):14.
Savage, MJ et al. A sensitive Aβ oligomer assay discriminates Alzheimer’s and aged control cerebrospinal fluid. J Neurosci. 2014;34(8):2884-2897.  

Sensitivity You Can Count On (SMCxPRO™ Immunoassay Platform)

Neuroscientists are often working with micro-volumes of blood plasmaNeuroscientists are often working with micro-volumes of blood plasma or cerebrospinal fluid (CSF) for analysis, requiring quantifiable data of low-abundant proteins with rapid precision. The new SMCxPRO™ platform is a highly sensitive instrument designed to fit seamlessly into your workflow and detect low-abundant proteins at the femtogram/mL level, serving your neuroscience research.

This compact benchtop solution offers:

  • High sensitivity (femtogram/mL)
  • Rapid analysis
  • Plate or bead-based assays
  • Compact: 14” W × 16” H × 17.5” D
  • Ready-made to fully customized kits
  • Access to over 600 antibody pairs

Learn more at EMDMillipore.com/smcxpro

 

VISUAL

 Visual analysis of fluorescently tagged cellular markers in peripheral blood provides major insights regarding progression and therapeutic intervention in neurological diseases. An imaging flow cytometer is a powerful tool that allows neuroscientists to monitor inflammation processes in disease models and clinical samples.

CHALLENGE

Tools and techniques are needed to monitor the central nervous system’s (CNS) response to injuries and neurological diseases.

> SOLUTION

Microscopy Combined With Flow Cytometry

Visually document cellular changes and further your mechanistic understanding of protective versus harmful immune responses with the use of imaging flow cytometers.

Imaging Flow Cytometers (Amnis®) — FlowSight® & ImageStream® Mark II

 By combining the speed, sensitivity, and phenotyping abilities of flow cytometry with the detailed imagery and functional insight of microscopy, the ImageStream®X MKII and FlowSight® instruments overcome the limitations of both techniques and open the door to an extensive range of novel applications for neuroscience discovery. Imaging flow cytometers are being used to study inflammation, neurologically important molecular localization and immune-neurological inter-relationships. Reports on hyperactivity of the innate immune system in Huntington’s disease1, monitoring changes in survival motor neuron protein in spinal muscular atrophy patients2, the effects of Rituximab in patients with multiple sclerosis3 are a few examples.

Highlighted Applications*

  • Internalization
  • Cell signaling
  • Intracellular trafficking
  • Morphology
  • Cell interactions
  • Autophagy
  • Cell death

 

Instruments

APPLICATION SPOTLIGHT

Neuroinflammation

NeuroinflammationThe central and peripheral nervous systems are equipped with an intricate damage response system that enables protection from pathogens, toxins and traumatic injury. However, that protective mechanism can cause chronic neuroinflammatory states that have been associated with the progression of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, Huntington’s disease, multiple sclerosis, ALS, as well as psychiatric disorders.4–8 Researchers face challenges in developing neuroprotective treatment strategies due to unknowns regarding the intricacies of protective versus harmful response mechanisms. With the use of ImageStream® Mark II, that combines microscopy with flow cytometry to visualize cells of the immune or nervous system, researchers can magnify up to 60X and observe morphology changes, co-localization and internalization of tagged markers, gaining a deeper understanding of neuroinflammation.

*The ImageStream® Mark II and FlowSight® systems are designed to be general-purpose platforms for cellular studies and are not limited to the applications illustrated in this brochure.

 

Instruments

TECHNOLOGY HIGHLIGHT

Discover Through Visualization

Amnis® Imaging Flow Cytometers

Quantifying Nuclear Translocation with Fluorescent Image Similarity
Translocation of NFκB from the cytoplasm to the nucleus of the cell is a key event in the response to the presence of cell stressors. Only imaging flow cytometers can analyze translocation quantitatively, in thousands of cells.

A closer look at NFκB signaling with 60× magnification
Here, THP-1 cells stimulated or not with LPS and stained with anti-NFκB and 7-AAD to counterstain the nucleus were collected on the ImageStream®X system using the 60× objective. The IDEAS® software similarity feature demonstrates binning of samples consistent with the FlowSight® histogram, and establishes the quality of visual detail that the ImageStream®X system can provide when needed for studies when greater detail is a benefit.

THP-1 cell line human, Cat. No. 88081201
Monoclonal anti-NFκB antibody produced in mouse, Cat. No. N8523
7-Aminoactinomycin D (7-AAD) fluorescent DNA stain, Cat. No. A9400

Discover Through Visualization

 

Custom Neuroscience Biomarker Assay Development

Your unique neuroscience research may demand tracking unique combinations of biomarkers. Our custom assay development service allows you to pick your assay platform and validation levels to meet your specific neuroscience biomarker discovery needs.

Get the degree of customization you need

  • Combine existing assays from our broadest collection of analytes available
  • Receive complete protocols, analytical validation and all the reagents you need in a single kit
  • Got an antibody? We can conjugate it to xMAP beads and validate for your Luminex system or your platform of choice
  • No antibody yet? We’ll develop one for you, carefully choosing immunogen and appropriate screening and validation

Whatever your project may be, get started today with a complimentary feasibility assessment.
Contact your local specialist at customassay@emdmillipore.com

 

Milli-Q®
Lab Water

Lab Water PurificationLab Water Purification

Much like having the appropriate assay is key to advancing research, having a consistent supply of appropriate water is key to every lab. Count on our portfolio of Milli-Q® water systems that are designed for a broad range of uses to meet any research need.

Superior ultrapure water — consistently — to the trace level:

The Milli-Q® IQ 7000 system provides superior ultrapure water consistently to the trace level with the combination of Jetpore® and IQnano® resin. You can fully rely on the system’s water purity for your critical experiments. And with the A10® TOC on-board monitoring, you’re spared from uncertainty or misinterpreting results.

MAKING HEADWAY

Driven by a desire to improve human health for all, we are building a network of discovery —creating connections, scientists-to-scientists, and sharing insights, ideas and expertise with the goal of advancing neuroscience research. Whether you are developing innovative predictive models, detecting novel protein interactions, or discovering unique biomarkers, working together we can solve the toughest challenges in neuroscience.

Our focus is working with you on tools to effectively discover, detect, and monitor biomarkers to advance your neuroscience research.

Join our network of discovery at
SigmaAldrich.com/neuroscience

 

Materials

     

Explore Application References

  1. Dobson, L et al. Laquinimod dampens hyperactive cytokine production in Huntington’s disease patient myeloid cells. J Neurochem. 2016;137(5):782-794.
  2. Arakawa, R et al. Imaging Flow Cytometry Analysis to Identify Differences of Survival Motor Neuron Protein Expression in Patients With Spinal Muscular Atrophy. Pediatr Neurol. 2016;61:70-75.
  3. Palanichamy, AJ et al. Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol. 2014;193(2):580-586.
  4. Ransohoff, RM. How neuroinflammation contributes to neurodegeneration. Science. 2016;353(6301):777-783.
  5. Bakunina, N et al. Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology. 2015;144(3):365–373.
  6. Crotti, A et al. The choreography of neuroinflammation in Huntington’s disease. Trends Immunol. 2015;36(6):364-373.
  7. Sekar, A et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530(7589):177-183.
  8. Jones, KL et al. Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. Mol Psychiatry. 2017;22(2):273-279.

 

 

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