Micro-rna, autoantibody and protein markers for diagnosis of neuronal injury

Abstract

Processes and materials are provided for the detection, diagnosis, or determination of the severity of a neurological injury or condition, including traumatic brain injury, multiple-organ injury, stroke, Alzeimer's disease, Pakinson disease and Chronic Traumatic Encephalopathy (CTE). The processes and materials include biomarkers detected or measured in a biological sample such as whole blood, serum, plasma, or CSF. Such biomarkers include Tau and GFAP proteins, their proteolytic breakdown products, brain specific or enriched micro-RNA, and brain specific or enriched protein directed autoantibodies. The processes and materials are operable to detect the presence of absence of acute, subacute or chronic brain injuries and predict outcome for the brain injury.

1 . A process for detecting a neurological condition in a subject comprising:
 measuring a quantity of one or more neuron specific biomarkers in a biological sample from the subject, wherein the synthesis of said biomarker is altered following an injury; and   detecting a neurological condition based on a ratio of the quantity one or more of said biomarkers in said biological sample.   
     
     
         2 . The process of  claim 1  wherein said condition is selected from the group comprising:
 brain injury, multiple-organ injury, stroke, neurodegenerative disease, including Alzeimer's disease, Parkinson's disease and Chronic Traumatic Encephalopathy (CTE), or. 
 
     
     
         3 . The process of  claim 1  wherein said biomarker is an autoantibody directed toward a protein, wherein said protein is: GFAP; Tau; S100β; βIII-tubulin; Neuroflilament light, medium or heavy polypeptide (NF-L, -M and -H); V-type proton ATPase; Gamma-enolase (NSE); vimentin; endophilin-A1; Microtubule-associated protein 2 (MAP-2); alpha-internexin; neuroserpin; neuromodulin; synaptotagmin-1; Voltage-gated potassium channel; collapsin response mediator proteins (CRMP-1 to 5); αII-spectrin; neurofascin; MBP; ubiquitin carboxyl-terminal esterase; Poly (ADP-ribose) polymerase (PARP); breakdown products thereof; derivatives thereof; or combinations thereof. 
     
     
         4 . The process of  claim 1  wherein said biomarker is a nucleic acid encoding at least a portion of a protein, wherein said protein is GFAP; αII-spectrin; an αII-spectrin breakdown product; neurofascin; MBP; MAP2; ubiquitin carboxyl-terminal esterase; a ubiquitin carboxyl-terminal hydrolase; a neuronally-localized intracellular protein; MAP-tau; C-tau; Poly (ADP-ribose) polymerase (PARP); a collapsin response mediator protein; breakdown products thereof, derivatives thereof, or combinations thereof. 
     
     
         5 . The process of  claim 1  wherein said biomarker is a at least a portion of a miRNA that regulates the expression of a protein, wherein said protein is GFAP; αII-spectrin; an αII-spectrin breakdown product; neurofascin; MBP; MAP2; ubiquitin carboxyl-terminal esterase; a ubiquitin carboxyl-terminal hydrolase; a neuronally-localized intracellular protein; MAP-tau; p53; SYTL1; calpastatin; Poly (ADP-ribose) polymerase (PARP); CAPN1, 2, or 6; IRS-1; SMAD5; a collapsin response mediator protein; synaptotagmin-1 or -9; Rho kinase; synapsin 1; syntaphilin; ATXN1; derivatives thereof; or combinations thereof. 
     
     
         6 - 8 . (canceled) 
     
     
         9 . The process of  claim 1  wherein said biomarker is a breakdown product of GFAP or Tau. 
     
     
         10 . (canceled) 
     
     
         11 . The process of  claim 1  or  9  wherein said biomarker is a breakdown product of human Tau (SEQ ID NO: 11) from cleavage C-terminal to amino acid 25, 44, 129, 157, 229, 421, or combinations thereof. 
     
     
         12 . The process of  claim 1  wherein biomarker is a breakdown product of rat Tau (SEQ ID NO: 5) from cleavage C-terminal to amino acid 43, 120, 220, 370, 412, or combinations thereof. 
     
     
         13 . The process of  claim 1  wherein said ratio is the concentration of said biomarker following said injury relative to the concentration of said biomarker in a control subject. 
     
     
         14 . (canceled) 
     
     
         15 . The process of  claim 1  wherein said biological sample is blood, serum, plasma, CSF, urine, saliva or tissue. 
     
     
         16 . The process of  claim 1  wherein said injury is induced by a compound. 
     
     
         17 - 23 . (canceled) 
     
     
         24 . A detection agent to a breakdown product of GFAP, said detection agent binding a portion of human GFAP within 10 amino acids of the cleavage site at amino acid position 59 or 383 in SEQ ID NO: 114. 
     
     
         25 . (canceled) 
     
     
         26 . A detection agent to a breakdown product of human Tau, said detection agent binding a human Tau (SEQ ID NO: 11) amino sequence within ten amino acids of the cleavage site at amino acid position 25, 44, 129, 157, 229, or 421. 
     
     
         27 . The detection agent of  claim 26  that binds an amino acid sequence within 10 amino acids C-terminal to Ser129, within 10 amino acids N-terminal to Va1229, within 10 amino acids N-terminal to Asp421, within 10 amino acids C-terminal to Lys44, within 10 amino acids N-terminal to Ser129, within 10 amino acids C-terminal to amino acid position 25, within 10 amino acids N-terminal to 25, within 10 amino acids N-terminal to 157, within 10 amino acids C-terminal to 157, within 10 amino acids N-terminal to Lys44, within 10 amino acids C-terminal to Va1229, within 10 amino acids C-terminal to Asp421. 
     
     
         28 - 33 . (canceled)