With the ever-increasing population of aged individuals at risk of developing

With the ever-increasing population of aged individuals at risk of developing Alzheimer disease there is an urgent need for a sensitive specific non-invasive diagnostic standard. Thus measuring total amounts of antigen or antibody following unmasking is critical. Here using a technique for dissociating antibody-antigen complexes we found significant differences in serum antibodies to amyloid-β between Alzheimer disease and aged-matched control subjects. While the current study demonstrates the relevance of measuring total antibody bound and unbound against amyloid-β in Alzheimer disease this technique may be applicable to diseases such as AIDS and hepatitis B where determination of antigen and antibody levels are important for disease diagnosis and assessing disease progression. 1999 Andreasen 2001). Aβ is the major protein component of the abnormal brain pathology the senile plaque that accumulates in specific brain regions of patients and is used for a definitive postmortem diagnosis (Murayama & Saito 2004 McKeel 2004). While Aβ1-42 failed to be a reliable biomarker in plasma attention was drawn to the potential of measuring auto-antibodies directed against Aβ. Thus the majority of recent efforts have focused on auto-antibodies Cefoselis sulfate against Aβ not only as a potential treatment for AD but as a reliable biomarker of AD (Blennow 2004). Naturally occurring antibodies against Aβ are found in the CSF and plasma of patients with AD as well as in healthy control subjects. Immunization of mice with Aβ1-42 and subsequent administration of these antibodies against Aβ into amyloid-β protein precursor transgenic mice (an animal model of AD) dramatically reduced amyloid plaque deposition neuritic dystrophy and astrogliosis most likely by enhancing Aβ1-42 clearance from brain (Schenk 1999 Wilcock 2001). A number of reports show Cefoselis sulfate that patients with AD have lower levels of serum anti-Aβ antibodies than healthy age-matched individuals (Weksler 2002 Du Cefoselis sulfate 2001). Other studies however indicate that the level of anti-Aβ antibody may be much higher in AD as compared to control. Mruthinti and colleagues (2004) for example reported that PLXNA1 affinity purified IgGs binding the peptide Aβ1-42 exhibited nearly four-fold higher titers in AD patients versus unaffected individuals. In addition Aβ antibody titers were negatively correlated with cognitive status such that more cognitively impaired individuals tended to exhibit higher anti-Aβ IgG titers (Mruthinti et al. 2004). The major difference between this and previous studies was that Mruthinti used affinity purified IgG. Nonetheless the vast majority of studies show little difference in Aβ-antibodies in sera from patients versus unaffected individuals (Hyman et al. 2001). In biological fluids antibodies and antigens are in a state of dynamic equilibrium between bound and unbound forms that is concentration dependent. Consequently the antigen may effectively mask a proportion of the corresponding antibody and limit both antibody and antigen detection. Under certain disassociating conditions this interaction can be interrupted thus freeing antibody and antigen and providing a more accurate analysis of both specific antibody titers and antigen concentration. Although antibody titers against a particular antigen in a given disease state may be strongly elevated only a Cefoselis sulfate fraction of the total amount is likely detectable via ELISA (enzyme linked immunoassay) due to interference by antigen-antibody complexes. In this case if the complexes are dissociated free antibody would be significantly elevated. For example if 4 units of antigen are circulating together with 5 units of antibody in one patient and 1 unit of antigen is usually circulating together with 2 units of antibody in another assuming that antibodies are bound both patients would be said to have Cefoselis sulfate 1 unit of free antibody detectable (Physique 1A). In contrast after dissociation of the antigen-antibody complexes (Physique 1B) these same patients would display 5 and 2 units of free antibody respectively. Physique 1 In dissociated samples unbound antigen-antibody complexes reveal increased disease-state antigens versus non-diseased counterparts. Therefore while non-dissociated samples offer no diagnostic value dissociated antigen and antibody values are discordant … The aim of this study is usually.