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

Nelly Joseph-Mathurin, Olène Dorieux, Stéphanie G. Trouche, Allal Boutajangout, Audrey Kraska, Pascaline Fontès, Jean Michel Verdier, Einar M. Sigurdsson, Nadine Mestre-Francés, Marc Dhenain

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Anti-amyloid beta (Aβ) immunotherapy provides potential benefits in Alzheimer's disease patients. Nevertheless, strategies based on Aβ1-42 peptide induced encephalomyelitis and possible microhemorrhages. 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 Aβ1-42 or Aβ-derivative (K6Aβ1-30). We followed anti-Aβ40 immunoglobulin G and M responses and Aβ levels in plasma. Invivo magnetic resonance imaging and histology were used to evaluate amyloidosis, neuroinflammation, vasogenic edema, microhemorrhages, and brain iron deposits. The animals responded mainly to the Aβ1-42 immunogen. This treatment induced immune response and increased Aβ 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 Aβ-immunization at prodromal stages of Alzheimer's disease, and should be monitored in clinical trials.

Original languageEnglish
Pages (from-to)2613-2622
Number of pages10
JournalNeurobiology of Aging
Volume34
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • ARIA (amyloid imaging related abnormalities)
  • Aging
  • Alzheimer's disease
  • Aβ-immunization
  • Choroid plexus
  • Iron
  • Lemur
  • MRI
  • Microcebus murinus
  • Microhemorrhages
  • Primate

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