Neural Proteins as Biomarkers for Nervous System Injury and Other Neural Disorders

Abstract

The present invention identifies biomarkers that are diagnostic of nerve cell injury and/or neuronal disorders. Detection of different biomarkers of the invention are also diagnostic of the degree of severity of nerve injury, the cell(s) involved in the injury, and the subcellular localization of the injury.

1 . A composition of biomarkers selected from one or more of the group consisting of βIII-tubulin, vesicular membrane protein (p24), neurensin-(p24), α-tubulin and synuclein, and isoforms thereof in a suitable medium. 
   
   
       2 . The composition of  claim 1  further comprising UCH-L1 and at least one proteolytic breakdown product of βIII-tubulin, synuclein or p24 polypeptide. 
   
   
       3 . A kit for diagnosing neural injury and/or neuronal disorders in a subject, the kit comprising:
 (a) a substrate for holding a biological sample isolated from a human subject suspected of having a damaged nerve cell,   (b) an agent that specifically and independently binds at least one of βIII-tubulin, vesicular membrane protein (p24), neurensin(p24), ubiquitin C-terminal hydrolase L1 (UCH-L1) or synuclein; and   (c) printed instructions for reacting the agent with the biological sample or a portion of the biological sample to detect the presence or amount of at least one marker in the biological sample.   
   
   
       4 . The kit of  claim 3 , wherein the substrate is hydrophobic, hydrophilic, charged, polar, or metal ions. 
   
   
       5 . The kit of  claim 3 , wherein the agent is an antibody, single or double stranded oligonucleotide, amino acid, protein, or peptide. 
   
   
       6 . The kit of  claim 3 , wherein the βIII-tubulin, neurensin(p24), UCH-L1 or synuclein is detected using an immunoassay. 
   
   
       7 . The kit of  claim 6 , wherein the immunoassay is an ELISA assay. 
   
   
       8 . The kit of  claim 7 , wherein the ELISA assay is a sandwich assay. 
   
   
       9 . The kit of  claim 3 , wherein the at least one of βIII-tubulin, neurensin(p24), UCH-L1 or synuclein is detected in blood or CSF. 
   
   
       10 . The kit of  claim 3 , wherein the neural injury is traumatic brain injury. 
   
   
       11 . The kit of  claim 3 , wherein the diagnosis of neural injury is indicated by a higher amount of at least one of βIII-tubulin, neurensin(p24), or synuclein in a CSF or blood sample of a subject suspected of having neural injury compared with amount of said biomarker in a respective sample from an uninjured subject. 
   
   
       12 . The kit of  claim 11 , wherein the blood sample is serum. 
   
   
       13 . The kit of  claim 12 , wherein the amount of synuclein in a subject serum sample is higher than in a serum sample from an uninjured subject. 
   
   
       14 . The kit of  claim 12 , wherein the amount of neurensin(p24), in the subject serum sample is higher than in a serum sample from an uninjured subject. 
   
   
       15 . The kit of  claim 12 , wherein the amount of βIII-tubulin in a subject serum sample is higher than in a serum sample from an uninjured subject. 
   
   
       16 . The kit of  claim 12 , wherein the amounts of synuclein, p24 and βIII-tubulin in a subject serum sample are higher than in a serum sample from an uninjured subject. 
   
   
       17 . The kit of  claim 12 , wherein the amounts of synuclein and neurensin(p24), in a subject serum sample are higher than in a serum sample from an uninjured subject. 
   
   
       18 . The kit of  claim 12 , wherein the amounts of neurensin(p24), and βIII-tubulin in a subject serum sample are higher than in a serum sample from an uninjured subject. 
   
   
       19 . The kit of  claim 11 , wherein increasing amounts of one or more of synuclein, neurensin(p24), and βIII-tubulin in a CSF or blood sample up to a period of at least 24 hr are indicative of severity of neural injury.