Amyloid beta immunization worsens iron deposits in the choroid plexus and cerebral microbleeds

Anti-amyloid beta (A beta) immunotherapy provides potential benefits in Alzheimer's disease patients. Nevertheless, strategies based on A beta(1-42) peptide induced encephalomyelitis and possible micro-hemorrhages. These outcomes were not expected from studies performed in rodents. It is critical to determine if other animal models better predict side effects of immunotherapies. Mouse lemur primates can develop amyloidosis with aging. Here we used old lemurs to study immunotherapy based on A beta(1-42) or A beta-derivative (K6A beta(1-30)). We followed anti-A beta(40) immunoglobulin G and M responses and A beta levels in plasma. In vivo magnetic resonance imaging and histology were used to evaluate amyloidosis, neuro-inflammation, vasogenic edema, microhemorrhages, and brain iron deposits. The animals responded mainly to the A beta(1-42) immunogen. This treatment induced immune response and increased A beta levels in plasma and also microhemorrhages and iron deposits in the choroid plexus. A complementary study of untreated lemurs showed iron accumulation in the choroid plexus with normal aging. Worsening of iron accumulation is thus a potential side effect of A beta-immunization at prodromal stages of Alzheimer's disease, and should be monitored in clinical trials. (C) 2013 Published by Elsevier Inc.