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ORIGINAL ARTICLE

Antibodies to ß-Amyloid Decrease the Blood-to-Brain Transfer of ß-Amyloid Peptide¹

Weihong Pan^*,2, Beka Solomon, Lawrence M. Maness^* and Abba J. Kastin^*

^* Veterans Affairs Medical Center and Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112; and
Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Ramat Aviv 69978, Tel-Aviv, Israel

Amyloid-ß peptides (Aß) play an important role in the pathophysiology of dementia of the Alzheimer’s type and in amyloid angiopathy. Aß 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 Aß have been developed in an effort to vaccinate against Alzheimer’s disease. These antibodies could interact with Aß in the peripheral blood, block the passage of Aß across the BBB, or prevent Aß deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Aß (¹²⁵I-Aß_1-40) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Aß after iv bolus injection. It also significantly decreased the accumulation of Aß 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-Aß_1-40 with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Aß into the brain after perfusion. Therefore, effective antibodies to Aß can reduce the influx of Aß_1-40 into the brain.

Key Words: ß-amyloid peptides • antibody • blood-brain barrier • vaccine • Alzheimer’s disease • mice