Frenkel D et al. (2005) Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease. J Clin Invest 115: 2423–2433

A novel potential vaccination treatment for Alzheimer's disease (AD) was recently described by Frenkel and colleagues. This new approach avoids the use of anti-amyloid-β (anti-Aβ) antibodies, which were found to cause meningoencephalitis in clinical trials.

Aβ-peptide fibrils are thought to have a key role in AD pathogenesis, and the researchers carried out a series of experiments in AD mouse models. They investigated the potential of glatiramer acetate (GA; currently used to treat multiple sclerosis), administered nasally in combination with a proteosome-based mucosal adjuvant known to be well tolerated in humans, to clear (Aβ) fibrils. Immunization with GA and the proteosome-based adjuvant resulted in a 73% reduction in total brain Aβ levels compared with controls (P <0.001). The combination of GA and the mucosal adjuvant had the advantage of producing potent therapeutic effects via a treatment that could be administered nasally rather than requiring invasive parenteral administration.

Immunohistochemical analysis revealed that animals treated with the nasal vaccination developed activated microglia that colocalized with Aβ plaques, and there was a strong correlation between the amount of microglial activation and the observed reduction in Aβ fibrils.

The authors propose that their results suggest a novel approach to immune therapy for AD that uses compounds that have been safely tested or used in humans. They note, however, that GA and the adjuvant have not yet been tested together in humans.