Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of Alzheimer's disease patients

Accumulation of Abeta protein in beta-amyloid deposits is a hallmark event in Alzheimer's disease (AD). Recent findings suggest anti-Abeta autoantibodies may have a role in AD pathology. However, a consensus has yet to emerge as to whether endogenous anti-Abeta autoantibodies are elevated, depr...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-04, Vol.280 (17), p.17458
Main Authors: Moir, Robert D, Tseitlin, Katya A, Soscia, Stephanie, Hyman, Bradley T, Irizarry, Michael C, Tanzi, Rudolph E
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - blood
Alzheimer Disease - immunology
Alzheimer Disease - pathology
Amyloid beta-Peptides - chemistry
Amyloid beta-Protein Precursor - chemistry
Autoantibodies - chemistry
Blotting, Western
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immunoblotting
Immunoglobulin G - chemistry
Male
Middle Aged
Oxidation-Reduction
Protein Isoforms
Risk Factors
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Summary:Accumulation of Abeta protein in beta-amyloid deposits is a hallmark event in Alzheimer's disease (AD). Recent findings suggest anti-Abeta autoantibodies may have a role in AD pathology. However, a consensus has yet to emerge as to whether endogenous anti-Abeta autoantibodies are elevated, depressed, or unchanged in AD patients. Whereas experiments to date have used synthetic unmodified monomeric Abeta (Abetamon) to test autoimmunity, up to 40% of the Abeta pool inB AD brain consists of low molecular weight oligomeric cross-linked beta-amyloid protein species (CAPS). Recent studies also suggest that CAPS may be the primary neurotoxic agent in AD. In the present study, AD and nondemented control plasma were analyzed for immunoreactivity to CAPS and Abetamon. Plasma of both nondemented and AD patients were found to contain autoantibodies specific for soluble CAPS. Nondemented control and AD plasmas demonstrated similar immunoreactivity to Abetamon. In contrast, anti-CAPS antibodies in AD plasma were found to be significantly reduced compared with nondemented controls (p=0.018). Furthermore, age at onset for AD correlated significantly (p=0.041) with plasma immunoreactivity to CAPS. These data suggest that autoantibodies to CAPS are depleted in AD patients and raise the prospect that immunization with anti-CAPS antibodies might provide therapeutic benefit for AD.
ISSN:0021-9258
1083-351X