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December 2004

DNA Vaccination May Open Up a New Avenue for Treatment of Alzheimer Disease

Arch Neurol. 2004;61(12):1832. doi:10.1001/archneur.61.12.1832

Accumulation of amyloid-β (Aβ40 − 42) peptides that are generated by proteolytic processing of amyloid precursor protein is widely considered to play a major role in the neurodegeneration of Alzheimer disease (AD), and the amelioration of amyloid burden is a hot target for the treatment of AD. Immunization by Aβ42 peptide has been demonstrated to lead to reduction of Aβ burden accompanied by improved cognitive performance in a mouse transgenic model of AD.1 This approach of Aβ42 peptide immunization has been applied in a clinical trial of patients with AD. About 300 patients with AD received multiple doses of the Aβ42 peptide with the adjuvant QS21. Although patients with higher antibody titer (20%) seemed to show a slowing of the cognitive decline, the program was discontinued owing to the fact that about 6% of treated patients developed autoimmune meningoencephalitis.2-4 This experience suggests that Aβ42 peptide immunization is potentially an effective treatment for AD, if the mechanisms of development of the meningoencephalitis are fully understood and development of meningoencephalitis can be avoided.

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