Summary
Active immunization with the amyloid-β (Aβ) peptide has been shown to decrease brain Aβ deposition in transgenic mouse models of Alzheimer’s disease (AD), and certain peripherally administered anti-Aβ antibodies mimic this effect. The mechanism(s) underlying these effects is under investigation. PDAPP mice represent a transgenic mouse model of AD. Interestingly, in young PDAPP mice that lack AD pathology, levels of CSF and plasma Aβ are strongly correlated and thus appear to be in equilibrium. In contrast, this correlation is absent in older PDAPP mice with plaques. We explored whether the presence in the periphery of a monoclonal anti- Aβ antibody (m266) directed against the central domain of Aβ could modify this equilibrium. Peripheral administration of m266 to PDAPP mice bound and sequestered all plasma AP and resulted in a rapid, massive increase in plasma Aβ as well as a reduction in Aβ deposition in the brain in chronically treated animals. Since amyloid plaques appear to abrogate the correlation between CNS and plasma Aβ, we assessed whether CNS to plasma Aβ efflux, as influenced by peripheral injection of m266, was indicative of brain amyloid load. Following intravenous administration of m266, we observed a rapid increase in plasma Aβ, and the magnitude of this increase was highly correlated with amyloid burden in the hippocampus and cortex of PDAPP mice. Together, these results suggest that there is a dynamic equilibrium between CNS and plasma Aβ and that certain anti-Aβ antibodies can act as a “peripheral sink” and alter this equilibrium.
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Holtzman, D.M., Bales, K.R., Paul, S.M., DeMattos, R.B. (2003). Effects of a Peripheral Anti-Aβ Antibody on Plasma and CNS Aβ Clearance. In: Selkoe, D.J., Christen, Y. (eds) Immunization Against Alzheimer’s Disease and Other Neurodegenerative Disorders. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59332-1_8
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DOI: https://doi.org/10.1007/978-3-642-59332-1_8
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