Antibodies to beta-amyloid decrease the blood-to-brain transfer of beta-amyloid peptide.

Abstract

Amyloid-beta peptides (Abeta) play an important role in the pathophysiology of dementia of the Alzheimer's type and in amyloid angiopathy. Abeta outside the CNS could contribute to plaque formation in the brain where its entry would involve interactions with the blood-brain barrier (BBB). Effective antibodies to Abeta have been developed in an effort to vaccinate against Alzheimer's disease. These antibodies could interact with Abeta in the peripheral blood, block the passage of Abeta across the BBB, or prevent Abeta deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Abeta (125I-Abeta(1-40)) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Abeta after iv bolus injection. It also significantly decreased the accumulation of Abeta in brain parenchyma. To confirm the in-vivo study and examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer was performed after incubation of 125I-Abeta(1-40) with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Abeta into the brain after perfusion. Therefore, effective antibodies to Abeta can reduce the influx of Abeta(1-40) into the brain.