Compositions and methods related to tauopathy

Abstract

Disclosed herein are isolated polypeptides, antibody preparations, treatment methods, diagnostic methods, and screening methods related to tauopathy. Generally, the isolated polypeptide includes a core pentapeptide, with the proviso that the isolated polypeptide is not a native full-length tau protein. Generally, the antibody preparations include antibody that specifically binds to SEQ ID NO:12. Generally, the treatment methods include administering to a subject a composition that includes the isolated polypeptide. Generally, the diagnostic methods includes contacting a sample from a subject with an antibody preparation that includes antibody that specifically binds to SEQ ID NO:12, and then detecting a ligand in the sample that specifically binds the antibody preparation. Generally, the screening method includes incubating a mixture of caspase-2, a labeled caspase-2 cleavage substrate, and a test compound under conditions effective to permit the caspase-2 to cleave the caspase-2 cleavage substrate, then determining whether the test compound inhibits cleavage of the substrate by caspase-2.

1 - 48 . (canceled) 
     
     
         49 . A method of detecting a product of caspase-2-mediated cleavage of tau in a subject, the method comprising:
 contacting a biological sample comprising cerebral spinal fluid from the subject; and   detecting the polypeptide of SEQ ID NO:13 in the biological sample.   
     
     
         50 . The method of  claim 49  wherein detecting SEQ ID NO:13 comprises:
 contacting the sample with an antibody preparation that specifically binds to SEQ ID NO:13; 
 allowing the antibody preparation to bind to the polypeptide of SEQ ID NO:13 in the biological sample; 
 removing unbound antibody preparation; and 
 detecting the antibody preparation that has bound to SEQ ID NO:13. 
 
     
     
         51 . The method of  claim 50  wherein the antibody preparation comprises a polyclonal antibody preparation. 
     
     
         52 . The method of  claim 51  further comprising quantifying SEQ ID NO:13 in the biological sample. 
     
     
         53 . The method of  claim 49  wherein the biological sample is a first biological sample and the method further comprises detecting the product of caspase-2-mediated cleavage of tau in a second sample obtained from the subject. 
     
     
         54 . The method of  claim 53  wherein detecting the product of caspase-2-mediated cleavage of tau in a second sample obtained from the subject comprises:
 contacting a second biological sample comprising cerebral spinal fluid from the subject; and 
 detecting the polypeptide of SEQ ID NO:13 in the second biological sample. 
 
     
     
         55 . The method of  claim 54  wherein detecting SEQ ID NO:13 in the second biological sample comprises:
 contacting the second biological sample with an antibody preparation that specifically binds to SEQ ID NO:13; 
 allowing the antibody preparation to bind to the polypeptide of SEQ ID NO:13 in the second biological sample; 
 removing unbound antibody preparation; and 
 detecting antibody preparation that has bound to SEQ ID NO:13 in the second biological sample. 
 
     
     
         56 . The method of  claim 54  further comprising quantifying SEQ ID NO:13 in the second biological sample. 
     
     
         57 . The method of  claim 54  wherein the first biological sample and the second biological sample are obtained from the subject at different times.