Toward modeling hemorrhagic and encephalitic complications of Alzheimer amyloid-beta vaccination in nonhuman primates

Current Opinion in Immunology
Sam Gandy, Lary C Walker

Abstract

The potential of amyloid-beta (Abeta) immunization as a disease-modifying therapy for Alzheimer's disease is limited by the occurrence of encephalitic side effects in a subset of treated patients. The encephalitis was not predicted from immunization studies in transgenic, Abeta-depositing mice. More recently, studies in these same mice indicate that passive immunization with certain anti-Abeta antibodies can induce microhemorrhage. Cerebral amyloid angiopathy (CAA) may play a key role in determining the risk for these complications. Because aged nonhuman primates (NHPs) have a more human-like immune system than rodents, and because NHPs naturally develop senile plaques and CAA with age, NHPs appear to be important, adjunctive models for assessing the efficacy and safety of immunotherapeutics for Alzheimer's disease. Conversely, the ability to model the complications of Abeta immunotherapy will be important for elucidating the bases of these complications, and for developing protocols that minimize or eliminate the risks of these serious adverse effects.

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Citations

Mar 15, 2005·Biochemical Pharmacology·Lary C WalkerSam Gandy
Jun 15, 2006·Alzheimer Disease and Associated Disorders·Robert P Brendza, David M Holtzman
Jun 1, 2006·Expert Review of Neurotherapeutics·Felix Mor, Alon Monsonego
Apr 7, 2009·Expert Opinion on Biological Therapy·Gregory A Jicha
Nov 10, 2009·Journal of Comparative Pathology·F Boudet
Oct 9, 2007·Nuclear Medicine and Biology·Chester A MathisWilliam E Klunk
Dec 15, 2016·Expert Opinion on Drug Discovery·Debby Van Dam, Peter Paul De Deyn
Jul 10, 2007·The FEBS Journal·Thomas Wisniewski, Einar M Sigurdsson
Sep 3, 2008·Journal of Neurochemistry·Daniel Alvarez-FischerPatrick P Michel
Jul 9, 2010·Progress in Neurobiology·Elisabetta Polazzi, Barbara Monti

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