Amyloid-β targeting immunisation in aged non-human primate (Microcebus murinus)

Abstract

Non-human primates have an important translational value given their close phylogenetic relationship to humans. Studies in these animals remain essential for evaluating efficacy and safety of new therapeutic approaches, particularly in aging primates that display Alzheimers disease (AD) -like pathology. With the objective to improve amyloid-{beta} (A{beta}) targeting immunotherapy, we investigated the safety and efficacy of an active immunisation with an A{beta} derivative, K6A{beta}1-30-NH2, in old non-human primates. Thirty-two aged (4-10 year-old) mouse lemurs were enrolled in the study, and received up to four subcutaneous injections of the vaccine in alum adjuvant or adjuvant alone. Even though antibody titres to A{beta} were not high, pathological examination of the mouse lemur brains showed significant reduction in intracellular A{beta} without inflammatory or haemorrhagic changes. Moreover, a trend for cognitive improvement was observed in the vaccinated primates, which was probably linked to A{beta} clearance. This A{beta} derivative vaccine appeared to be safe as a prophylactic measure based on the brain analyses and because it did not appear to have detrimental effects on the general health of these old animals.