Assays to detect neurodegeneration
Methods of measuring the amount of singly- or multiply-phosphorylated p217+ tau protein in a sample are provided. Methods of detecting or diagnosing tauopathies, methods of determining the effectiveness of a treatment of a tauopathy, and methods of determining whether a subject is suitable for anti-p217+ tau antibody therapy are also provided. Also described are antibodies for use in the methods and kits comprising the antibodies.
1. An isolated antibody or antigen binding fragment thereof that binds tau comprising:
(a) an immunoglobulin heavy chain comprising a heavy chain complementarity determining region (HCDR) 1, HCDR2 and HCDR3 comprising amino acid sequences of SEQ ID NOs: 12, 13 and 14, respectively; and
(b) an immunoglobulin light chain comprising a light chain complementarity determining region (LCDR) 1, LCDR2 and LCDR3 comprising amino acid sequences of SEQ ID NOs: 15, 16 and 17, respectively.
2. The isolated antibody or antigen binding fragment thereof of claim 1 wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region that is at least 95% identical to SEQ ID NO: 18 and a light chain variable region that is at least 95% identical to SEQ ID NO: 19.
3. The isolated antibody or antigen binding fragment thereof of claim 1 wherein the antibody or antigen binding fragment thereof comprises:
(a) an immunoglobulin heavy chain comprising a HCDR1, HCDR2 and HCDR3 consisting of amino acid sequences of SEQ ID NOs: 12, 13 and 14, respectively; and
(b) an immunoglobulin light chain comprising LCDR1, LCDR2 and LCDR3 consisting of amino acid sequences of SEQ ID NOs: 15, 16 and 17, respectively.
4. The isolated antibody or antigen binding fragment thereof of claim 3 wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region that is at least 95% identical to SEQ ID NO: 18-and a light chain variable region that is at least 95% identical to SEQ ID NO: 19.
5. The isolated antibody or antigen binding fragment thereof of claim 1 wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising amino acid sequence of SEQ ID NO: 18 and a light chain variable region comprising amino acid sequence of SEQ ID NO: 19.
6. The isolated antibody or antigen binding fragment thereof of claim 5 wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region consisting of amino acid sequence of SEQ ID NO: 18 and a light chain variable region consisting of amino acid sequence of SEQ ID NO: 19.