Tau immunotherapy

1. A method of identifying an antibody comprising:

(a) immunizing a non-human animal with human tau (SEQ ID NO: 1) or a fragment thereof comprising residues 25-44 of SEQ ID NO: 1 to induce antibodies;

(b) screening induced antibodies to select antibodies that bind to human tau (SEQ ID NO: 1) within amino acid residues 25-44 of SEQ ID NO: 1; and

(c) identifying a selected antibody that competes for binding to SEQ ID NO: 1 with a reference antibody, wherein the reference antibody comprises:

(i) a heavy chain variable region having an amino acid sequence comprising SEQ ID NO: 10, and

(ii) a light chain variable region having an amino acid sequence comprising SEQ ID NO: 16.

2. The method of claim 1 , wherein step (b) comprises screening induced antibodies to identify an antibody binding within amino acids 28-33 of SEQ ID NO: 1.

3. The method of claim 1 , wherein the immunization is performed with a fragment consisting of amino acid residues 25-44 of SEQ ID NO: 1, optionally linked to a carrier.

4. The method of claim 1 , wherein the screening is performed by determining binding of the induced antibodies to a series of overlapping peptides spanning human tau.

5. The method of claim 1 , wherein the screening is performed by determining binding of the induced antibodies to a series of deletion mutants of human tau.

6. The method of claim 1 , wherein the screening is performed by alanine scanning mutagenesis.

7. The method of claim 1 , further comprising:

administering the identified antibody to a non-human transgenic animal expressing a tau transgene, and determining whether the identified antibody inhibits or delays at least one sign or symptom of Alzheimer's disease in the non-human transgenic animal.

8. The method of claim 1 , further comprising producing a humanized form of the identified antibody, the method comprising:

(a) synthesizing a nucleic acid encoding a humanized heavy chain comprising CDRs of a heavy chain of the identified antibody and a nucleic acid encoding a humanized light chain comprising CDRs of a light chain of the identified antibody; and

(b) expressing the nucleic acids in a host cell to produce a humanized antibody.

9. The method of claim 1 , wherein the identified antibody stains Alzheimer's Disease fibrillar pathological structures.

10. The method of claim 9 , wherein the Alzheimer's Disease fibrillar pathological structures comprise one or more of tau-positive neuritic plaques, neuropil threads, and neurofibrillary tangles.

11. The method of claim 1 , wherein the identified antibody is immunoreactive to one or more phosphorylated tau epitopes.

12. The method of claim 11 , wherein the one or more phosphorylated tau epitopes comprises one or more of:

(i) serine 202 and threonine 205,

(ii) serine 212 and threonine 214, and

(iii) serine 396.