Immunotherapy in a Rabbit Model of Alzheimer’s Disease

Author(s): Diana S. Woodruff-Pak, Christina Shriver, Alexis Agelan, Joanne M. Manns, Richard Coico

Journal Name: Drug Delivery Letters

Volume 2 , Issue 1 , 2012


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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, , temporal cortex, parietal cortex, frontal cortex, Anti-A antibodies, Alzheimer’s disease, TH2 helper, polysorbate-80, Histopathology

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Article Details

VOLUME: 2
ISSUE: 1
Year: 2012
Published on: 06 May, 2012
Page: [14 - 21]
Pages: 8
DOI: 10.2174/2210304x11202010014

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