Reduced levels of amyloid β-peptide antibody in Alzheimer disease

Objective: To investigate whether it was possible to detect the presence and different levels of naturally occurring anti-beta -amyloid (A beta) antibodies in the CSF of patients with AD and age-matched controls by employing a sensitive ELISA. Background: Immunization with preaggregated amyloid beta -peptide (A beta (1-42)) and administration of antibodies against A beta into amyloid precursor protein APP(V717F)-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 A beta clearance from brain. Methods: A sensitive ELISA was performed to detect levels of naturally occurring anti-A beta antibodies in the CSF of patients with AD and age-matched controls. Additionally, an immunoprecipitation assay was performed to confirm that naturally occurring anti-A beta antibodies also exist in the human blood. Result: Naturally occurring antibodies directed against A beta were found in the CSF and plasma of patients with AD and healthy control subjects. Moreover, CSF anti-A beta antibody titers are significantly lower in patients with AD compared with healthy control subjects. Conclusion: Naturally occurring antibodies directed against A beta exist in human CSF and plasma. The CSF anti-A beta antibody titers may be helpful in better understanding the effects of future immunologic therapies for AD.