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

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. In vivo 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.
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https://hal.umontpellier.fr/hal-01977714
Contributeur : Nadine Mestre-Frances <>
Soumis le : vendredi 11 janvier 2019 - 08:20:28
Dernière modification le : mercredi 14 octobre 2020 - 04:05:01

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Nelly Joseph-Mathurin, Olène Dorieux, Stephanie Trouche, Allal Boutajangout, Audrey Kraska, et al.. Amyloid beta immunization worsens iron deposits in the choroid plexus and cerebral microbleeds. Neurobiology of Aging, Elsevier, 2013, 34 (11), pp.2613-2622. ⟨10.1016/j.neurobiolaging.2013.05.013⟩. ⟨hal-01977714⟩

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