Intracerebroventricular passive immunization with anti-Aβ antibody in Tg2576

• Published in: Journal of neuroscience research 2003-10, Vol.74 (1), p.142-147
• Main Authors: Chauhan, Neelima B., Siegel, George J.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; cerebral hemorrhage; immunotherapy; inflammation; intracerebroventricular passive immunization
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10721

Current Alzheimer's disease (AD) research has established the fact that excessive genesis of Aβ derived from amyloidogenic processing of β‐amyloid (Aβ) precursor protein is fundamental to AD pathogenesis. There has been considerable interest in using immunization strategies for clearing excessive Aβ. Studies in animal models of AD have shown that active immunizations or systemic passive immunizations reduced cerebral plaque load and improved behavioral deficits. However, clinical translation of an active immunization strategy was interrupted because of evidence for meningoencephalitis produced in some patients who received Aβ vaccine. Studies in animal models have shown perimicrovascular hemorrhages and inflammation after sustained systemic immunizations in animals with vascular amyloid. In this light, our data showing the effects of a single intracerebroventricular (ICV) injection of anti‐Aβ in the Alzheimer's Swedish mutant model Tg2576 are intriguing. We have previously demonstrated that a single ICV injection of anti‐Aβ into the third ventricle of 10‐month‐old Tg2576 mice reduced cerebral plaques, reversed Aβ‐induced depletion of presynaptic SNAP‐25, and abolished astroglial activation as seen 1 month post‐injection (Chauhan and Siegel [2002] J. Neurosci. Res. 69:10–23). The present report demonstrates that a single ICV injection of 10 μg anti‐Aβ in 10‐month‐old Tg2576 mice reduced cerebral plaques, with decreased inflammation at this stage as evidenced by a reduced number of interleukin‐1β‐positive microglia surrounding Congophilic plaques. Moreover, at this particular age, no microhemorrhage was discernible, as evidenced by the absence of hemosiderin deposition after a single ICV injection of anti‐Aβ. This is the first report demonstrating absence of microhemorrhage and reduced inflammation after the ICV introduction of anti‐Aβ in Tg2576 mice at 10 months of age. These facts indicate that, although invasive, ICV injection of anti‐Aβ may be a safer method of vaccination in AD, possibly through reducing the vascular exposure to antibody. Further studies are warranted to determine the lasting effects of a single ICV anti‐Aβ injection in animals with and without abundant plaque burden and at older ages. © 2003 Wiley‐Liss, Inc.