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

Abstract

To characterize antibodies produced in humans in response to Aβ42 vaccination, we carried out immunohistochemical examinations of the brains of both transgenic mice and human patients with β-amyloid pathology. We collected sera from patients with Alzheimer disease who received a primary injection of pre-aggregated Aβ42 followed by one booster injection in a placebo-controlled study. Antibodies in immune sera recognized β-amyloid plaques, diffuse Aβ deposits and vascular β-amyloid in brain blood vessels. The antibodies did not cross-react with native full-length β-amyloid precursor protein or its physiological derivatives, including soluble Aβ42. These findings indicate that vaccination of AD patients with Aβ42 induces antibodies that have a high degree of selectivity for the pathogenic target structures. Whether vaccination to produce antibodies against β-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.

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Hock, C., Konietzko, U., Papassotiropoulos, A. et al. Generation of antibodies specific for β-amyloid by vaccination of patients with Alzheimer disease. Nat Med 8, 1270–1275 (2002). https://doi.org/10.1038/nm783

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