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Abeta immunization in aged vervet monkeys reduces Abeta levels in brain and CSF



Abeta immunization in aged vervet monkeys reduces Abeta levels in brain and CSF



Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 133 5



Amyloid beta (Abeta) immunization lowers cerebral Abeta in APP tg mice. A recent human clinical trial of Abeta immunization resulted in meningoencephalitis in17/300 AD patients, perhaps due to the recognition of the human Abeta peptide as a self-antigen. Non-human primates have the same Abeta sequence as humans and develop plaques with aging, so we immunized monkeys with Abeta peptide. Five aged (16-25 yr) Caribbean vervet monkeys were given 8 s.c. injections of Abeta peptide with CFA/IFA over 265 days. Baseline and periodic plasma and CSF samples were collected from the 5 immunized monkeys and from 5 aged controls. By Day 42, all immunized monkeys had plasma Abeta titers (e.g., 406 micrograms/ml +- 317 at Day 251) that labeled plaques in human AD and APP tg mouse brain, recognized Abeta1-7, and recognized monomeric and oligomeric Abeta but not full-length APP nor APP C-terminal fragments. Low Abeta titers were observed in CSF as well (e.g., 151 ng/ml +-113 at Day 251). Abetax-40 and Abeta-total levels were elevated in plasma of immunized monkeys. Abetax-40 levels in CSF were decreased by apprx50% at Days 100, 251 and at sacrifice (Day 301). The 4 immunized monkeys and 2 controls were euthanized; frozen brain tissues from 10 age-matched controls were provided. Insoluble AbetaX-42 was decreased 67% (p=0.035) in the immunized animals compared to controls; insoluble Abetax-40 was unchanged. Abeta42-reactive plaques were detected in each of 2 brain regions in 11/13 controls whereas no plaques were detected in any of 6 brain regions examined for each of the 4 immunized vervets. No T cell response or inflammation was found. Thus, Abeta immunization in Vervet monkeys results in anti-Abeta titers, increased peripheral Abeta and decreased CNS Abeta levels, confirming the results observed in APP tg mice for the first time in non-human primates.

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