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 96% identity to SEQ ID NO:1.
2. The antibody fragment of claim 1 , wherein the nucleic acid has at least 97% identity to SEQ ID NO: 1.
3. The antibody fragment of claim 1 , wherein the nucleic acid has at least 98% identity to SEQ ID NO:1.
4. The antibody fragment of claim 1 , wherein the nucleic acid has at least 99% identity to SEQ ID NO:1.
5. The antibody fragment of claim 1 , wherein the nucleic acid has 100% identity to SEQ ID NO:1.
6. 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 Degeneration (FTP), wherein the binding molecule comprises an amino acid sequence encoded by a nucleic acid, wherein the nucleic acid has at least 96% identity to SEQ ID NO:1.
7. The binding molecule of claim 6 , wherein the nucleic acid has at least 97% identity to SEQ ID NO:1.
8. The binding molecule of claim 6 , wherein the nucleic acid has at least 98% identity to SEQ ID NO:1.
9. The binding molecule of claim 6 , wherein the nucleic acid has at least 99% identity to SEQ ID NO:1.
10. The binding molecule of claim 6 , wherein the nucleic acid has 100% identity to SEQ ID NO:1.
11. A method of binding TDP-43 associated with ALS comprising contacting a composition that comprises TDP-43 associated with ALS with an antibody fragment or binding molecule of any one of claim 1 or 6 .
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. An imaging composition specific for TDP-43 associated with ALS comprising an antibody fragment or a binding molecule of any one of claim 1 or 6 conjugated to an imaging agent.