Generation of antibodies specific for β-amyloid by vaccination of patients with Alzheimer disease

• Published in: Nature medicine Vol. 8; no. 11; pp. 1270 - 1275
• Main Authors: Nitsch, Roger M, Hock, Christoph, Konietzko, Uwe, Papassotiropoulos, Andreas, Wollmer, Axel, Streffer, Johannes, von Rotz, Ruth C, Davey, Gabriela, Moritz, Eva
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-11-2002
• Subjects: Aged; Alzheimer Vaccines - administration & dosage; Alzheimer Vaccines - immunology; Amyloid beta-Peptides - immunology; Animals; Antibodies - blood; Antibodies - immunology; Base Sequence; Cross Reactions; DNA Primers; Female; Humans; Immune Sera; Male; Mice; Mice, Transgenic
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm783

To characterize antibodies produced in humans in response to Abeta42 vaccination, we carried out immunohistochemical examinations of the brains of both transgenic mice and human patients with beta-amyloid pathology. We collected sera from patients with Alzheimer disease who received a primary injection of pre-aggregated Abeta42 followed by one booster injection in a placebo-controlled study. Antibodies in immune sera recognized beta-amyloid plaques, diffuse Abeta deposits and vascular beta-amyloid in brain blood vessels. The antibodies did not cross-react with native full-length beta-amyloid precursor protein or its physiological derivatives, including soluble Abeta42. These findings indicate that vaccination of AD patients with Abeta42 induces antibodies that have a high degree of selectivity for the pathogenic target structures. Whether vaccination to produce antibodies against beta-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.