Methods and materials for detecting c9orf72 hexanucleotide repeat expansion positive frontotemporal lobar degeneration or c9orf72 hexanucleotide repeat expansion positive amyotrophic lateral sclerosis

Abstract

This document provides methods and materials for detecting C9ORF72 hexanucleotide (GGGGCC) (SEQ ID NO: 3) repeat expansion positive (C9 + ) frontotemporal lobar degeneration or C9 + amyotrophic lateral sclerosis. For example, methods and materials related to using anti-(GP) 8 (SEQ ID NO: 2) antibodies to identify mammals (e.g., humans) having C9 + FTLD or C9 + ALS are provided.

1 . A method for identifying a mammal having an expanded hexanucleotide (GGGGCC) repeat in a noncoding region of at least one C9ORF72 allele, wherein said method comprises:
 (a) contacting a biological sample obtained from said mammal with an anti-polyGP antibody under conditions wherein a polyGP polypeptide present within said biological sample and said anti-polyGP antibody form a polyGP polypeptide/anti-polyGP antibody complex,   (b) detecting said polyGP polypeptide/anti-polyGP antibody complex, and   (c) classifying said mammal as having said expanded hexanucleotide (GGGGCC) repeat.   
     
     
         2 . The method of  claim 1 , wherein said mammal is a human. 
     
     
         3 . The method of  claim 1 , wherein said biological sample is a cerebrospinal fluid sample. 
     
     
         4 . The method of  claim 1 , wherein said biological sample is a blood sample. 
     
     
         5 . The method of  claim 1 , wherein the binding affinity of said anti-polyGP antibody for a (GP) 8  polypeptide is between 10 6  mol −1  and 10 12  mol −1 . 
     
     
         6 . The method of  claim 1 , wherein the binding affinity of said anti-polyGP antibody for a (GP) 8  polypeptide is between 10 6  mol −1  and 10 12  mol −1 , and wherein the binding affinity of said anti-polyGP antibody for a (PGP) 8  polypeptide is less than 10 3  mol −1 . 
     
     
         7 . A method for identifying a human as having C9 +  neurological condition, wherein said method comprises:
 (a) contacting a biological sample obtained from a human with an anti-polyGP antibody under conditions wherein a polyGP polypeptide present within said biological sample and said anti-polyGP antibody form a polyGP polypeptide/anti-polyGP antibody complex, 
 (b) detecting said polyGP polypeptide/anti-polyGP antibody complex, and 
 (c) classifying said human as having a C9 +  neurological condition. 
 
     
     
         8 . The method of  claim 7 , wherein said biological sample is a cerebrospinal fluid sample. 
     
     
         9 . The method of  claim 7 , wherein said biological sample is a blood sample. 
     
     
         10 . The method of  claim 7 , wherein the binding affinity of said anti-polyGP antibody for a (GP) 8  polypeptide is between 10 6  mol −1  and 10 12  mol −1 . 
     
     
         11 . The method of  claim 7 , wherein the binding affinity of said anti-polyGP antibody for a (GP) 8  polypeptide is between 10 6  mol −1  and 10 12  mol −1 , and wherein the binding affinity of said anti-polyGP antibody for a (PGP) 8  polypeptide is less than 10 3  mol −1 . 
     
     
         12 . The method of  claim 7 , wherein said C9 +  neurological condition is a C9 +  FTLD. 
     
     
         13 . The method of  claim 7 , wherein said C9 +  neurological condition is a C9 +  ALS. 
     
     
         14 - 21 . (canceled)