nCounter® Neuropathology Panels

Perform comprehensive multiplex gene expression analysis with 770 genes included in six fundamental themes of neurodegeneration: neurotransmission, neuron-glia interaction, neuroplasticity, cell structure integrity, neuroinflammation and metabolism.

  • neuro-cell-illustrations_v3-09.pngDeveloped for research of Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Huntington’s Disease and other neurological disorders
  • Includes unique cell typing feature for measuring the abundance of five important cell types including neurons, astrocytes, microglia, oligodendrocytes and endothelial cells
  • Customizable with up to 30 additional user-defined genes with Panel Plus option

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Genes included in the Neuropathology Panels provide unique cell profiling data for measuring the abundance1 of five important cell types including neurons, astrocytes, microglia, oligodendrocytes and endothelial cells. The table below summarizes each cell type represented in the panels along with the gene content qualified through current literature references.

Cell Type Cell Description Associated Human Genes Associated Mouse Genes

neuron.png

Neurons

Neuronal cell death and loss of function is a key driver of neurodegeneration. DLX1, DLX2, GRM2, ISLR2, SLC17A6, TBR1 Dix1, Dix2, Grm2, Isir2, Sic17a6, Tbr1

astrocytes.png

Astrocytes

Astrocytes represent the most numerous and diverse glial cells in the brain, responsible for a wide variety of homeostatic functions including modulation of synaptic function, network regulation, energy metabolism, neurotransmitter synthesis, among others. The loss of normal homeostatic functions and gain of toxic functions is implicated in the onset and progression of neurodegeneration. ALDH1L1, EGFR, ENTPD2, GDPD2, ITGA7, KIAA1161, NWD1, SOX9 Aldh1l1, Egfr, Entpd2, Gdpd2, Itga7, Al464131, Nwd1, Sox9

microglia.png

Microglia

Microglia represent a CNS resident myeloid cell population ontologically distinct from peripheral macrophages/monocytes. Microglia act to maintain brain homeostasis, contribute to neuroplasticity, and serve as a first line of innate immune defense in the brain. Their activation may serve as an early indicator of pathology, while chronic microglia activation or dysfunction may contribute to disease pathogenesis. GPR84, IRF8, LRRC25, NCF1, TLR2, TNF, AIF1, TMEM119, ITGAM, CX3CR1, P2RY12, SPI1 Gpr84, Irf8, Lrrc25, Ncf1, Tlr2, Aif1, Tmem119, Itgam, Cx3cr1, P2ry12, Spi1

oligo.png

Oligodendrocytes

Oligodendrocytes are highly specialized glial cells that synthesize myelin to ensheath axons of the central nervous system. Injury to or loss of oligodendrocyte function puts neuronal network function and survival at risk. Oligondendrocyte injury and death and axonal demyelination are hallmarks of some devastating neurological diseases. BCAS1, ERBB3, FA2H, GAL3ST1, GJB1, GSN, MYRF, NINJ2, PLLP, PLXNB3, PRKCQ, SOX10, UGT8 Bcas1, Erbb3, Fa2h, Gal3st1, Gjb1, Gsn, Myrf, Ninj2, Pllp, Plxnb3, Prkcq, Sox10, Ugt8a

endo.png

Endothelial Cells

Endothelial cells form the blood-brain barrier and play a critical role in protecting the central nervous system from dangerous pathogens. Endothelial cells are equipped with a defense system against oxidative stress and their dysfunction can release inflammatory and neurotoxic agents in the CNS. CLDN5, EMCN, ESAM, FLT1, ICAM2, LSR, MYCT1, NOSTRIN, TIE1 Cldn5, Emcn, Esam, Flt1, Icam2, Lsr, Myct1, Nostrin, Tie1

 

1 Danaher P. et al. Gene expression markers of Tumor Infiltrating Leukocytes JITC 2017

Functional annotations for 23 fundamental pathways and processes were assigned across all genes in the Neuropathology Panels allowing for a practical view of important aspects of the onset and progression of neurodegenerative disease.

 

Fundamental Themes of Neurodegeneration Description Annotation Human Genes Mouse Genes
Neurotransmission Neurotransmission is the core function of the nervous system, and is critically impaired in neurodegenerative disorders Transmitter Release 165 164
Vesicular Trafficking 156 155
Transmitter Response/Reuptake 148 147
Transmitter Synthesis and Storage 59 59
Neuron-Gila Interaction Gila protect neurons and maintain homeostasis within the CNS, making their function crucial to brain health and the prevention of neurodegenerative disorders. Myelination 47 47
Secretion of Trophic Factors 48 48
Neuroplasticity, Development, and Aging The ability of the nervous system to form new connections during development and throughout life in response to environmental changes or injury. The brain's ability to repair itself declines with age and loss of plasticity is characteristic of neurodegenerative disorders. Growth Factors 150 149
Angiogenesis 78 82
Chromatin Modification 62 62
Apoptosis 61 59
Compartmentalization and Structural Integrity Neurodegenerative diseases are characterized by a relentlessly progressive loss of the functional and structural integrity of the nervous system. Neuronal Cytoskeleton 17 17
Axon and Dendrite Structure 160 159
Inter-Neuron Connectivity 166 166
Tissue Integrity 45 44
Neuroinflammation Inflammation within the central nervous system which may be initiated by neuronal death, aberrant protein aggregation, infection, traumatic brain injury, toxic metabolites or autoimmunity. Activated Microgila 92 97
Matrix Remodelling 5 7
Pro-Inflmmatory Cytokines 52 50
Metabolism Impaired metabolic pathways, including RNA transcription/splicing, protein translation/degradation, carbohydrate metabolism, lipid metabolism, autophagy, and oxidative stress are hallmarks and causative agents in neurodegenerative disorders. Unfolded Protein Response 48 47
Oxidative Stress 91 91
Transcription and mRNA Splicing 47 46
Autophagy 33 33
Carbohydrate Metabolism 44 44
Lipid Metabolism 41 41

 

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Selected Panel References

The below publications were used as references in the creation of this panel.

Glaab, Schneider Comparative pathway and network analysis of brain transcriptome changes during adult aging and in Parkinson’s disease. Neurobiology of Disease 74, 1-13 (2015).

Loring J.F., Wen X., Lee J.M., Seilhamer J., Somogyi R. A Gene Expression Profile of Alzheimer’s Disease. DNA and Cell Biology 20, 683-695 (2001).

Kudo, Lili C., Parfenova, Liubov, Vi, Nancy, Lau, Kimbley, Pomakian, Justine, Valdmanis, Paul, Rouleau, Guy A., Vinters, Harry V., Wiedau-Pazos, Martina, Karsten, Stanislav L. Integrative gene-tissue microarray-based approach for identification of human disease biomarkers: application to amyotrophic lateral sclerosis. Human Molecular Genetics 19, 3233-3253 (2010).

Holtman, IR Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis. Acta Neuropathologica Communications 3, 0001-0018 (2015).

Ferrari, Raffaele, Forabosco, Paola, Vandrovcova, Jana, Botía, Juan A, Guelfi, Sebastian, Warren, Jason D, Momeni, Parastoo, Weale, Michael E, Ryten, Mina, Hardy, John Frontotemporal dementia: insights into the biological underpinnings of disease through gene co-expression network analysis. Molecular Neurodegeneration 11, 21 (2016).

Mariani, Elisa, Frabetti, Flavia, Tarozzi, Andrea, Pelleri, Maria Chiara, Pizzetti, Fabrizio, Casadei, Raffaella Meta-Analysis of Parkinson’s Disease Transcriptome Data Using TRAM Software: Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene Expression. PloS One 11, e0161567 (2016).

Rosen, Ezra Y., Wexler, Eric M., Versano, R., Coppola, G., Gao, F., Winden, Kellen D., Oldham, Michael C., Martens, L., Zhou, P., Farese, Robert V., Geschwind, Daniel H. Functional Genomic Analyses Identify Pathways Dysregulated by Progranulin Deficiency, Implicating Wnt Signaling. Neuron 71, 1030-1042 (2011).

Chiu, Isaac M, Morimoto, Emiko T A, Goodarzi, Hani, Liao, Jennifer T, O’Keeffe, Sean, Phatnani, Hemali P, Muratet, Michael, Carroll, Michael C, Levy, Shawn, Tavazoie, Saeed, Myers, Richard M, Maniatis, Tom A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Reports 4, 385-401 (2013).

Hickman Suzanne E, Kingery Nathan D, Ohsumi Toshiro K, Borowsky Mark L, Wang Li-chong, Means Terry K, El Khoury Joseph The microglial sensome revealed by direct RNA sequencing. Nature Neuroscience 16, 1896-1905 (2013).

Zhang, Gaiteri, Bodea, Wang, McElwee, Podtelezhnikov, Zhang, Xie, Tran, Dobrin, Fluder, Clurman, Melquist, Narayanan, Suver, Shah, Mahajan, Gillis, Mysore, MacDonald, Lamb, Bennett, Molony, Stone, Gudnason, Myers, Schadt, Neuma Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease. Cell 153, 707-720 (2013).

Twine, Natalie A, Janitz, Karolina, Wilkins, Marc R, Janitz, Michal Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer’s disease. PloS One 6, e16266 (2011).

Lee Cheol-Koo, Weindruch Richard, Prolla Tomas A. Gene-expression profile of the ageing brain in mice. Nature Genetics 25, 294-297 (2000).

Jiang, C H, Tsien, J Z, Schultz, P G, Hu, Y The effects of aging on gene expression in the hypothalamus and cortex of mice. Proceedings of the National Academy of Sciences of the United States of America 98, 1930-4 (2001).

nCounter Neurobiology Publications

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Feature

Specifications

Number of Targets 770 (Human), 770 (Mouse) including internal reference genes
Standard Input Material (No amplification required) 25 ng-300 ng
Low Input Material As little as 1 ng with nCounter Low Input Kit and Panel specific primer pools (sold separately)
Sample Type(s) FFPE-derived RNA, total RNA, fragmented RNA, PBMC's, whole blood/plasma, iPS cells, cerebrospinal fluid
Customizable Add up to 30 unique genes with Panel-Plus
Time to Results Approximately 24 hours
Data Analysis nSolverTM Analysis Software, Advanced Analysis Modules

 

Product Product Description Quantity Catalog Number
nCounter® Human Neuropathology Panel Includes 770 genes, including 10 internal reference genes for data normalization 12 Reactions XT-CSO-HNROP1-12
nCounter® Mouse Neuropathology Panel Includes 770 genes, including 10 internal reference genes for data normalization 12 Reactions XT-CSO-MNROP1-12

Pre-order an nCounter Neuropathology panel or request gene list here

For Research Use Only. Not for use in diagnostic procedures.