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

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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.