Chronic mucosal administration of certain proteins is known to decrease organ-specific autoimmune processes in several autoimmune models, including those affecting the CNS. In AD, local inflammatory responses frequently occur in the vicinity of plaques; thus, Cindy Lemere and colleagues reasoned that mucosal administration of Aβ could prevent or reduce the deleterious effects associated with plaque-induced inflammation (519.6). To test their hypothesis, Aβ peptide or control proteins were administered either orally or intranasally to PD-APP tg mice on a weekly basis from ~5 to 12 months of age, and the animals' brains were analyzed immunohistochemicalyl and biochemically. Oral administration of Aβ failed to suppress inflammation and did not alter plaque burden, whereas nasal administration of Aβ1-40 at 25 mg/week caused a dramatic 50-60 percent decrease in plaque burden. Activated microglia were found in those plaques that remained, indicating that the peri-plaque inflammatory response was not suppressed. Serum anti-Aβ antibodies were found in some oral, and eight out of nine nasally treated animals, with antibodies being highest in the nasally treated mice which showed reduction in plaque burden. These results together with those of the Elan group (519.5) confirm that immunization with Aβ can reduce plaque pathology and suggest that optimization of mucosal delivery may offer an attractive therapeutic route.
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