Antigen-antibody dissociation in Alzheimer disease: a novel approach to diagnosis.
With the ever-increasing population of aged individuals at risk of developing Alzheimer's disease (AD), there is an urgent need for a sensitive, specific, non-invasive, and diagnostic standard. The majority of efforts have focused on auto-antibodies against amyloid-beta (Abeta) protein, both as a potential treatment, and a reliable biomarker of AD pathology. Naturally occurring antibodies against Abeta are found in the CSF and plasma of patients with AD as well as healthy control subjects. To date, differences between diseased and control subjects have been highly variable. However, some of the antibody will be in preformed antigen-antibody complexes and the extent and nature of such complexes may provide a potential explanation for the variable results reported in human studies. 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 Abeta between AD and aged-matched control subjects. While the current study demonstrates the relevance of measuring total antibody, bound and unbound, against Abeta in AD, this technique may be applicable to diseases such as acquired immune deficiency syndrome and hepatitis B where determination of antigen and antibody levels are important for disease diagnosis and assessing disease progression.
Gustaw
Katarzyna A
KA
Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA.
Garrett
Matthew R
MR
Lee
Hyoung-Gon
HG
Castellani
Rudy J
RJ
Zagorski
Michael G
MG
Prakasam
Annamalai
A
Siedlak
Sandra L
SL
Zhu
Xiongwei
X
Perry
George
G
Petersen
Robert B
RB
Friedland
Robert P
RP
Smith
Mark A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000134:cerebrospinal fluid / Q000302:isolation & purification; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000097:blood / Q000134:cerebrospinal fluid; D000941:Antigens / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D007158:Immunologic Techniques; D051379:Mice; D008875:Middle Aged
D016229:Amyloid beta-Peptides; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000941:Antigens