Immunotherapy for Alzheimer's disease: from anti-β-amyloid to tau-based immunization strategies

Immunotherapy
Francesco PanzaAlberto Pilotto

Abstract

The exact mechanisms leading to Alzheimer's disease (AD) are largely unknown, limiting the identification of effective disease-modifying therapies. The two principal neuropathological hallmarks of AD are extracellular β-amyloid (Aβ), peptide deposition (senile plaques) and intracellular neurofibrillary tangles containing hyperphosphorylated tau protein. During the last decade, most of the efforts of the pharmaceutical industry were directed against the production and accumulation of Aβ. The most innovative of the pharmacological approaches was the stimulation of Aβ clearance from the brain of AD patients via the administration of Aβ antigens (active vaccination) or anti-Aβ antibodies (passive vaccination). Several active and passive anti-Aβ vaccines are under clinical investigation. Unfortunately, the first active vaccine (AN1792, consisting of preaggregate Aβ and an immune adjuvant, QS-21) was abandoned because it caused meningoencephalitis in approximately 6% of treated patients. Anti-Aβ monoclonal antibodies (bapineuzumab and solanezumab) are now being developed. The clinical results of the initial studies with bapineuzumab were equivocal in terms of cognitive benefit. The occurrence of vasogenic edema after bapineuzumab, an...Continue Reading

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Methods Mentioned

BETA
transgenic
glycosylation
protein folding
imaging techniques

Clinical Trials Mentioned

NCT00667810
NCT00676143
NCT00574132
NCT00575055
NCT00905372
NCT00904683

Software Mentioned

Octapharma
EXPEDITION2
EXPEDITION EXT

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