Immunotherapy in a Rabbit Model of Alzheimer’s Disease

Diana      S. Woodruff-Pak; Christina      Shriver; Alexis      Agelan; Joanne      M. Manns; Richard      Coico

doi:10.2174/2210304x11202010014

Abstract

To investigate immunotherapy in non-rodent model of Alzheimer’s disease (AD), 14 rabbits were fed a cholesterol/ copper regimen for 10 weeks (“hypercholesterolemic” or “AD model rabbits”), and 4 rabbits were fed normally (“control rabbits”). Six or 8 weeks after diet initiation, 10 hypercholesterolemic and 4 control rabbits were injected with conjugated Aβ1-42-peptide mixed with Freund’s complete adjuvant and boosted every two weeks with 4 additional doses in Freund’s incomplete adjuvant. Serum antibody titers were measured using an Aβ1-42-specific ELISA from blood. Brain Aβ was analyzed with immunohistochemistry. Anti-Aβ antibodies doubled from approximately 2.6 to 5.2 ng/ml. Even with this relatively low increase in anti-Aβ antibodies, there was a significant reduction in intracellular brain Aβ. Pathology is present in AD model rabbits by 4 weeks after diet initiation. Future studies of immunotherapy should begin earlier in disease progression that is comparable to preclinical AD in humans for greater reduction of brain Aβ.

Keywords: Cholesterol, copper, Aβ, temporal cortex, parietal cortex, frontal cortex, Anti-A antibodies, Alzheimer’s disease, TH2 helper, polysorbate-80, Histopathology