ABSTRACT
The presence of pre-existing natural antibodies against Alzheimer's disease (AD) pathological proteins might interfere with immune responses to therapeutic vaccination with these proteins. We aimed to compare levels of antibodies in CSF and serum: We observed higher reactivity of natural tau-reactive antibodies towards phosphorylated bovine tau protein than to human recombinant (non-phosphorylated) tau protein. Males with MCI-AD had higher amounts of these antibodies than corresponding controls. Concentrations of antibodies were lower in females with the MCI-AD than in control females. These findings may have implications for tau vaccination trials.
Subject(s)
Alzheimer Disease/immunology , Autoantibodies/analysis , Sex Characteristics , tau Proteins/immunology , Aged , Alzheimer Disease/blood , Alzheimer Disease/cerebrospinal fluid , Animals , Antibody Specificity , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Cattle , Cognitive Dysfunction/blood , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/immunology , Dementia/blood , Dementia/cerebrospinal fluid , Dementia/immunology , Female , Humans , Male , Middle Aged , Phosphoproteins/chemistry , Phosphoproteins/immunology , Phosphorylation , Protein Processing, Post-Translational , Recombinant Proteins/immunology , Reproducibility of Results , Species Specificity , tau Proteins/chemistryABSTRACT
The presence of natural tau-reactive antibodies was reported in human blood. In this study, we isolated and characterized natural tau-reactive antibodies occurring in IVIG product Flebogamma, plasma of patients with Alzheimer's disease (AD) and older cognitively normal persons (controls). Using blotting immunoassays and ELISA, we showed reactivity of antibodies obtained from IVIG and controls against a recombinant fragment of tau (155-421aa) and aggregates present in brains of AD patients. In contrast, antibodies isolated from plasma of AD patients reacted mainly with the recombinant full-length tau form and tau monomeric forms in brain tissue.
Subject(s)
Alzheimer Disease/blood , Immunoglobulin G/blood , Immunoglobulins, Intravenous/blood , Immunoglobulins, Intravenous/immunology , tau Proteins/immunology , Aged , Aged, 80 and over , Alzheimer Disease/immunology , Alzheimer Disease/pathology , Alzheimer Disease/therapy , Brain/metabolism , Female , Humans , Immunoglobulin G/classification , Immunoglobulins, Intravenous/metabolism , Male , Middle Aged , PhosphorylationABSTRACT
Natural antibodies are now widely studied for their therapeutical potential. Therefore, their isolation and subsequent characterization is desired. Here, we describe an isolation method for natural anti-tau antibodies from human plasma by utilization of affinity chromatography with epoxy-activated copolymer resin. The evalution of isolation efficiency and avidity of isolated antibodies is decribed by modified indirect ELISA assay.
