Antibody based reagents that specifically recognize neurodegenerative disease related forms of the protein TDP-43
The invention relates to antibodies, antibody fragments and binding agents that specifically recognize TDP-43 associated with frontotemporal dementia (FTD), but not TDP-43 associated with amyotrophic lateral sclerosis (ALS) or TDP-43 associated with healthy human brain tissue, and antibodies, antibody fragments and binding agents that specifically recognize TDP-43 associated with ALS, but not TDP-43 associated FTD or TDP-43 associated with healthy human brain tissue.
1. An antibody fragment comprising an amino acid sequence encoded by a nucleic acid, wherein the nucleic acid has at least 97% identity to SEQ ID NO:11.
2. A method of binding TDP-43 associated with ALS comprising contacting a composition that comprises TDP-43 associated with ALS with the antibody fragment of claim 1 .
3. The method of claim 2 , wherein the TDP-43 associated with ALS is in a cell.
4. The method of claim 2 , wherein the TDP-43 associated with ALS is in brain tissue.
5. An imaging composition specific for TDP-43 associated with ALS comprising the antibody fragment of claim 1 conjugated to an imaging agent.
6. The antibody fragment of claim 1 , wherein the nucleic acid has at least 98% identity to SEQ ID NO:11.
7. The antibody fragment of claim 1 , wherein the nucleic acid has at least 99% identity to SEQ ID NO:11.
8. The antibody fragment of claim 1 , wherein the nucleic acid has 100% identity to SEQ ID NO:11.
9. A binding molecule that binds to TAR DNA binding protein 43 (TDP-43) associated with Amyotrophic Lateral Sclerosis (ALS) and does not bind TDP-43 from healthy human brain tissue or TDP-43 associated with Frontotemporal Dementia (FTD), wherein the binding molecule comprises an amino acid sequence encoded by a nucleic acid, wherein the nucleic acid has at least 97% identity to SEQ ID NO: 11.
10. An imaging composition specific for TDP-43 associated with ALS comprising the binding molecule of claim 9 conjugated to an imaging agent.
11. A method of binding TDP-43 associated with ALS comprising contacting a composition that comprises TDP-43 associated with ALS with the binding molecule of claim 9 .
12. The method of claim 11 , wherein the TDP-43 associated with ALS is in a cell.
13. The method of claim 11 , wherein the TDP-43 associated with ALS is in brain tissue.
14. The binding molecule of claim 9 , wherein the nucleic acid has at least 98% identity to SEQ ID NO:11.
15. The binding molecule of claim 9 , wherein the nucleic acid has at least 99% identity to SEQ ID NO:11.
16. The binding molecule of claim 9 , wherein the nucleic acid has 100% identity to SEQ ID NO:11.