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(American Journal of Pathology. 2004;165:283-297.)
© 2004 American Society for Investigative Pathology

Alzheimer’s Disease Aß Vaccine Reduces Central Nervous System Aß Levels in a Non-Human Primate, the Caribbean Vervet

Cynthia A. Lemere^*, Amy Beierschmitt, Melitza Iglesias^*, Edward T. Spooner^*, Jeanne K. Bloom^*, Jodi F. Leverone^*, Jessica B. Zheng^*, Timothy J. Seabrook^*, Dora Louard, Diana Li^*, Dennis J. Selkoe^*, Roberta M. Palmour and Frank R. Ervin

From the Center for Neurologic Diseases,^* Department of Neurology, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts; the Behavioral Sciences Foundation Caribbean Primate Laboratory, Saint Kitts, Eastern Caribbean; and McGill University School of Medicine, Montreal, Canada

Amyloid ß (Aß) protein immunotherapy lowers cerebral Aß and improves cognition in mouse models of Alzheimer’s disease (AD). Here we show that Caribbean vervet monkeys (Chlorocebus aethiops, SK) develop cerebral Aß plaques with aging and that these deposits are associated with gliosis and neuritic dystrophy. Five aged vervets were immunized with Aß peptide over 10 months. Plasma and cerebral spinal fluid (CSF) samples were collected periodically from the immunized vervets and five aged controls; one monkey per group expired during the study. By Day 42, immunized animals generated plasma Aß antibodies that labeled Aß plaques in human, AD transgenic mouse and vervet brains; bound Aß1–7; and recognized monomeric and oligomeric Aß but not full-length amyloid precursor protein nor its C-terminal fragments. Low anti-Aß titers were detected in CSF. Aßx-40 levels were elevated 2- to 5-fold in plasma and decreased up to 64% in CSF in immunized vervets. Insoluble Aßx-42 was decreased by 66% in brain homogenates of the four immunized animals compared to archival tissues from 13 age-matched control vervets. Aß42-immunoreactive plaques were detected in frontal cortex in 11 of the 13 control animals, but not in six brain regions examined in each of the four immunized vervets. No T cell response or inflammation was observed. Our study is the first to demonstrate age-related Aß deposition in the vervet monkey as well as the lowering of cerebral Aß by Aß vaccination in a non-human primate. The findings further support Aß immunotherapy as a potential prevention and treatment of AD.

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