Work

[P‐190]: AB derivatives as potentially safer vaccines for Alzheimer's disease

Year: 2005

Type: article

Abstract: Prior to the termination of the AN1792 trial due to encephalitis in some patients, we proposed that immunization with shorter Aβ derivatives was likely to be safer for human use (Am. J. Pathol., 159, 2001). All our vaccines have improved cognition in AD model Tg mice while eliciting variable immune response and reducing brain amyloid burden to different degrees (J.Neurosci. 24, 2004). 1) To determine the therapeutic benefit of K6Aβ1-30 in 2 year old Tg2576 mice with treatment starting at 11- vs. 19 months. 2) To assess the immune response and therapeutic effect of our vaccines in Microcebus murinus, a lemur primate that develops plaques and tangles as seen in AD. Mice were immunized with K6Aβ1-30 in alum adjuvant which promotes a humoral immune response. At 2 years of age, sensorimotor and cognitive tests were performed, and brains then processed for amyloid burden measurements. Young lemurs were immunized with Aβ1-42 and several non-toxic Aβ homologs in alum and bled at various time points between injections. Older lemurs are currently going through behavioral assessment prior to vaccination. In the mice, K6Aβ1-30 improved cognition when therapy was initiated at 11 months but not at 19 months. Amyloid burden analysis is underway. Cerebral bleeding has not been observed in brains from mice with high antibody titer examined so far. In the lemurs, all the peptides elicited a moderate to robust IgM titer. Aβ1-42 and K6Aβ1-30 resulted in a high IgG titer similar to the mouse response. Aβ1-30{E18E19} produced a low IgG reponse as in the mouse. K6Aβ1-30{E18E19} gave rise to a strong IgG titer whereas in the mouse this derivative elicited a low IgG titer. Bleeds at 5 months after last injection are in progress. The mouse findings indicate that immunotherapy at an old age may not be beneficial. The immune response in the mouse vs. the lemur primate differs for some of the Aβ homolog vaccines.

Source: Alzheimer s & Dementia

DOI: 10.1016/j.jalz.2005.06.249