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From the Departments of Pharmacology and Toxicology (Drs. Du, Lin, Gao, and Paul), Neurology (Dr. Farlow), and Psychiatry (Dr. Paul), Indiana University School of Medicine, Indianapolis; Department of Neurology (Drs. Dodel and Oertel), Philipps University, Marburg; Dementia Research Section and Memory Clinic (Drs. Hampel, Buerger, and Moeller), Ludwig-Maximilians University, Munich, Germany; and Neuroscience Discovery Research (K. Bale and Dr. Paul), Department of Statistical and Mathematical Sciences (Dr. Eastwood), Lilly Research Laboratories, Eli Lilly, Indianapolis, IN.
Address correspondence and reprint requests to Dr. Y. Du, Department of Pharmacology and Toxicology, Indiana University Medical School, 635 Barnhill Dr., Indianapolis, IN 46285; e-mail: ydu{at}iupui.edu
Objective: — To investigate whether it was possible to detect the presence and different levels of naturally occurring anti-ß-amyloid (Aß) antibodies in the CSF of patients with AD and age-matched controls by employing a sensitive ELISA.
Background: — Immunization with preaggregated amyloid ß-peptide (Aß1–42) and administration of antibodies against Aß into amyloid precursor protein APPV717F– transgenic mice (an animal model of AD) have recently been reported to dramatically reduce amyloid plaque deposition, neuritic dystrophy, and astrogliosis, most likely by enhancing Aß clearance from brain.
Methods: — A sensitive ELISA was performed to detect levels of naturally occurring anti-Aß antibodies in the CSF of patients with AD and age-matched controls. Additionally, an immunoprecipitation assay was performed to confirm that naturally occurring anti-Aß antibodies also exist in the human blood.
Result: — Naturally occurring antibodies directed against Aß were found in the CSF and plasma of patients with AD and healthy control subjects. Moreover, CSF anti-Aß antibody titers are significantly lower in patients with AD compared with healthy control subjects.
Conclusion: — Naturally occurring antibodies directed against Aß exist in human CSF and plasma. The CSF anti-Aß antibody titers may be helpful in better understanding the effects of future immunologic therapies for AD.
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