Other groups soon confirmed the beneficial effects of active immunization in other transgenic lines and showed that vaccination can reverse spatial memory deficits in APP and presenilin/APP mice.93,94 Strikingly, behavioral performance often improved more than brain Aβ levels or plaque pathology, with deficits in some lines being almost entirely normalized.17 Subsequently, it was found that passive immunization of anti-Aβ antibodies peripherally also reduced amyloid deposition.95,96 Indeed, multiple studies have shown that even short-term administration of anti-Aβ antibodies improves performance in tests of learning and memory.97 Improvements in behavioral performance with passive immunization strategies also occur even when no detectible effect is seen on deposits of plaque amyloid. For example, Dodart et al.98 gave weekly injections of the anti-Aβ monoclonal antibody m266 for 6 weeks to 24-month-old PDAPP mice and found that behavioral impairments were essentially normalized despite there being no effects on plaque pathology. Indeed, even a single injection of this antibody to 11-month-old mice produced beneficial effects on behavior that were apparent after 1 day of treatment.98 Similar effects have been observed with a different monoclonal antibody in Tg2576 mice.99
