Redox-reactive autoantibodies in Alzheimer's patients' cerebrospinal fluids: preliminary studies.
Oxidation of cerebrospinal fluid (CSF) causes differential unmasking of autoantibodies in control CSF vs. that obtained from postmortem CSF samples from autopsy confirmed Alzheimer's disease (AD) cases. This study demonstrates that normal CSF from both living patients and from non-demented autopsy cases contains redox-reactive autoantibodies with specificities that include antiphospholipid antibodies (aPL). In contrast, CSF from autopsy confirmed AD subjects contained little or no redox-reactive aPL autoantibodies. Tests using an in vitro rat synaptosome model showed that the oxidized CSF autoantibodies from a normal individual can cause ERK1/2 phosphorylation at a level consistent with reports of pathogenic changes found in brain tissues from AD patients. The decrease or absence of redox-reactive antibodies in CSF from Alzheimer's patients suggests that these antibodies may have been previously unmasked by the oxidative conditions that exist in the CNS in AD patients. These unmasked autoantibodies could then bind to neuronal tissues and possibly participate in the initial cascade leading to the dementia in Alzheimer's. To our knowledge, this is the first description of resident autoantibodies with the potential to cause brain cell damage documented in CSF without a breech in the blood-brain barrier. The untimely and inappropriate physiological unmasking of these redox-reactive autoantibodies in AD patients CSF may represent a valuable biomarker for diagnosis and progression of this and perhaps other neurodegenerative diseases which also have oxidative stress components. These novel autoantibody observations may stimulate thoughts about additional therapeutic approaches and warrant similar studies for other neurodegenerative diseases.
McIntyre
John A
JA
HLA-Vascular Biology Laboratory, St Francis Hospital and Health Care Centers, Beech Grove, IN 46107, USA. john.mcintyre@ssfhs.org
Chapman
Joab
J
Shavit
Efrat
E
Hamilton
Ronald L
RL
Dekosky
Steven T
ST
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism; D017152:Antibodies, Antiphospholipid / Q000134:cerebrospinal fluid* / Q000276:immunology; D017209:Apoptosis; D001323:Autoantibodies / Q000134:cerebrospinal fluid* / Q000276:immunology; D001327:Autoimmune Diseases / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010084:Oxidation-Reduction
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D015415:Biomarkers; D048052:Mitogen-Activated Protein Kinase 3