Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears beta-amyloid in a mouse model of Alzheimer disease

Amyloid beta-peptide (A beta) appears to play a key pathogenic role in Alzheimer disease (AD). Immune therapy in mouse models of AD via A beta immunization or passive administration of A beta antibodies markedly reduces A beta levels and reverses behavioral impairment. However, a human trial of A beta immunization led to meningoencephalitis in some patients and was discontinued. Here we show that nasal vaccination with a proteosome-based adjuvant that is well tolerated in humans plus glatiramer acetate, an FDA-approved synthetic copolymer used to treat multiple sclerosis, potently decreases A beta plaques in an AD mouse model. This effect did not require the presence of antibody, as it was observed in B cell-deficient (Ig mu-null) mice. Vaccinated animals developed activated microglia that colocalized with A beta fibrils, and the extent of microglial activation correlated strongly with the decrease in A beta fibrils. Activation of microglia and clearing of A beta occurred with the adjuvant alone, although to a lesser degree. Our results identify a novel approach to immune therapy for AD that involves clearing of A beta through the utilization of compounds that have been safely tested on or are currently in use in humans.