A method of isolating a monoclonal antibody specific for a disorder-associated pathological variant form of an endogenous protein comprising: (a) subjecting a sample from a culture of memory B cells from a subject who is phenotypically healthy but affected with or at risk of developing a neurological disorder characterized by pathological protein structures of the pathological variant form of the endogenous protein, or a patient with a clinically unusually stable disease course of the disorder to a specimen displaying pathological structures of the pathological variant form of the endogenous protein; (b) identifying in the sample the presence of an antibody which binds to said specimen but not to corresponding tissue of a healthy subject without such pathological structures; (c) obtaining the immunoglobulin gene repertoire for antibodies from said memory B cells of the sample which has been identified to contain antibodies which bind to said specimen but not to the corresponding tissue of a healthy subject without such pathological structures comprising the steps of: (i) obtaining mRNA from said memory B cells; (ii) obtaining cDNA from the mRNA of step (i); and (iii) using primer extension reaction to amplify from said cDNA the fragments corresponding to the heavy chains and the kappa/lambda light chains of said antibodies; (d) using the HC and LC sequences obtained in (c) to express said antibodies; and (e) isolating the antibody which specifically binds to pathologically altered tissue derived from a human patient or animal model of the disorder, wherein the tissue comprises pathological protein structures of the protein but not to tissue of a healthy subject without such pathological structures. (a) subjecting a sample from a culture of memory B cells from a subject who is phenotypically healthy but affected with or at risk of developing a neurological disorder characterized by pathological protein structures of the pathological variant form of the endogenous protein, or a patient with a clinically unusually stable disease course of the disorder to a specimen displaying pathological structures of the pathological variant form of the endogenous protein; (b) identifying in the sample the presence of an antibody which binds to said specimen but not to corresponding tissue of a healthy subject without such pathological structures; (c) obtaining the immunoglobulin gene repertoire for antibodies from said memory B cells of the sample which has been identified to contain antibodies which bind to said specimen but not to the corresponding tissue of a healthy subject without such pathological structures comprising the steps of: (i) obtaining mRNA from said memory B cells; (ii) obtaining cDNA from the mRNA of step (i); and (iii) using primer extension reaction to amplify from said cDNA the fragments corresponding to the heavy chains and the kappa/lambda light chains of said antibodies; (i) obtaining mRNA from said memory B cells; (ii) obtaining cDNA from the mRNA of step (i); and (iii) using primer extension reaction to amplify from said cDNA the fragments corresponding to the heavy chains and the kappa/lambda light chains of said antibodies; (d) using the HC and LC sequences obtained in (c) to express said antibodies; and (e) isolating the antibody which specifically binds to pathologically altered tissue derived from a human patient or animal model of the disorder, wherein the tissue comprises pathological protein structures of the protein but not to tissue of a healthy subject without such pathological structures.