Provided are novel human-derived dipeptide repeat (DPR) specific antibodies as well as synthetic variants and biotechnological derivatives thereof, preferably capable of binding C9ORF72 DPRs, as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for DPRs and DPR proteins such C9ORF72 DPRs are also disclosed. The antibody of the present invention can be used in pharmaceutical and diagnostic compositions for DPR protein-targeted immunotherapy and diagnostics.